Travis E. Grotz

Prognostic factors in Merkel cell carcinoma: Analysis of 240 cases

BACKGROUND Knowledge regarding behavior of and prognostic factors for Merkel cell carcinoma (MCC) is limited. OBJECTIVE We sought to further understand the characteristics, behavior, prognostic factors, and optimal treatment of MCC. METHODS A multicenter, retrospective, consecutive study of patients with known primary MCC was completed. Overall survival and survival free of locoregional recurrence were calculated and statistical analysis of characteristics and outcomes was performed. RESULTS Among the 240 patients, the mean age at diagnosis was 70.1 years, 168 (70.0%) were male, and the majority was Caucasian. The most common location was head and neck (111, 46.3%). Immunosuppressed patients had significantly worse survival, with an overall 3-year survival of 43.4% compared with 68.1% in immunocompetent patients. In our study, patients with stage II disease had improved overall survival versus those with stage I disease, in a statistically significant manner. Patients with stage III disease had significantly worse survival compared with stage I and with stage II. Primary tumor size did not predict nodal involvement. CONCLUSION The data presented represent one of the largest series of primary MCC in the literature and confirm that MCC of all sizes has metastatic potential, supporting sentinel lymph node biopsy for all primary MCC. Because of the unpredictable natural history of MCC, we recommend individualization of care based on the details of each patients tumor and clinical presentation.

Hepatic epithelioid haemangioendothelioma: is transplantation the only treatment option?

BACKGROUND Hepatic epithelioid haemangioendothelioma (HEH) is a rare vascular neoplasm with unpredictable clinical behaviour. AIM To compare overall survival (OS) and disease-free survival (DFS) between liver resection (LR) and orthotopic liver transplantation (OLT) for the treatment of HEH. METHODS Retrospective review of 30 patients with HEH treated at Mayo Clinic during 1984 and 2007. RESULTS Median age was 46 years with a female predominance of 2:1. Treatment included LR (n= 11), OLT (n= 11), chemotherapy (n= 5) and no treatment (n= 3). LR was associated with a 1-, 3- and 5-year OS of 100%, 86% and 86% and a DFS of 78%, 62% and 62%, respectively. OLT was associated with a 1-, 3- and 5-year OS of 91%, 73% and 73% and a DFS 64%, 46% and 46%, respectively. Metastases were present in 37% of patients but did not significantly affect OS. Important predictors of a favourable OS and DFS were largest tumour ≤ 10 cm and multifocal disease with ≤ 10 nodules. CONCLUSION LR and OLT achieve comparable results in the treatment of HEH. LR is appropriate for patients with resectable disease and favourable prognostic factors. OLT is appropriate for patients with unresectable disease and possibly those with unfavourable prognostic factors. Metastases may not be a contraindication to surgical treatment.

Regional immunity in melanoma: immunosuppressive changes precede nodal metastasis

In order to characterize the degree of immunosuppression in regional immunity in patients with melanoma, we used immunohistochemistry to analyze markers of T-cell subtype and polarity, costimulation, dendritic cell maturation, monocytes, lymphatic vasculature, and angiogenesis. Specifically, we analyzed expression of CD4, CD8, CD14, CD40, CD86, CD123, HLA-DR, IL-10, LYVE, VEGFR3, and VEGF-C in lymph nodes. We compared sentinel lymph nodes with and without metastasis from patients with melanoma with both infection inflamed (reactive) and dormant human lymph nodes. There were no differences demonstrated between sentinel lymph nodes with or without metastasis from patients with melanoma in any of the markers that were tested. Both groups of sentinel lymph nodes had fewer CD8+ T cells than either set of control nodes. Whereas the infection inflamed lymph nodes demonstrated Th2 polarity, the dormant lymph nodes demonstrated Th1 polarity. In conclusion, changes in regional immunity appeared to precede metastasis in melanoma. Whether there was tumor present in sentinel lymph nodes or not, these nodes demonstrated a marked decrease in cytotoxic T cells compared with both sets of controls. Furthermore, the control lymph nodes used for comparison can significantly impact interpretation, as the dormant and reactive lymph nodes markedly varied in their immune profiles. These immunologic changes may explain the successful metastasis of melanoma in the midst of the immune environment of the sentinel lymph node, and lend insights into the mechanisms of lymphatic metastases in other solid malignancies.

Adult intussusception in the last 25 years of modern imaging: is surgery still indicated?

BackgroundBecause most adult intussusceptions are reportedly due to malignancy, operative treatment is recommended. With current availability of computed tomography, we questioned the role of mandatory operative exploration for all adult intussusceptions.MethodsThis study is a retrospective review of all adults treated from 1983 to 2008 at a large tertiary referral center for intussusception.ResultsOne hundred ninety-six patients had intussusception over the 25-year study period. Computed tomography was obtained in 60% of patients. Neoplasms [malignant, (21%); benign, (24%)] were the commonest etiology; 30% cases were idiopathic. One hundred twenty (61%) patients underwent operative treatment for intussusception. Six of the 58 idiopathic or asymptomatic cases were operated on with negative findings in all. Palpable mass (OR 4.56, p < 0.035), obstructive symptoms (OR 9.13, p < 0.001) or obstruction (OR 9.67, p < 0.001), GI bleeding (OR 14.41, p < 0.001), and a lead point on computed tomography (OR 10.08, p < 0.001) were associated with the need for operation.ConclusionIn the current era of computed tomography, idiopathic or asymptomatic intussusception is being seen more commonly; however, the majority of adult intussusceptions still have pathologic lead points. From our experience, all patients with palpable mass, obstructive symptoms or obstruction, gastrointestinal bleeding, or a lead point on computed tomography should undergo operative exploration.

Surveillance strategies for gastrointestinal stromal tumors

Although only 10–30% of gastrointestinal stromal tumors (GISTs) are clinically malignant, all have some degree of malignant potential. The management of high risk patients should be evidence based. However, prospective data and a consensus for guidelines concerning the screening of asymptomatic high risk patients and surveillance following multidisciplinary treatment do not exist. This review provides an overview of GIST, with an emphasis on the available data regarding screening and surveillance of certain populations with GISTs. J. Surg. Oncol. 2011; 104:921–927.

The prognostic role of the preoperative absolute lymphocyte count and absolute monocyte count in patients with resected advanced melanoma.

Objectives:Published data have reported that components of the peripheral blood are significant prognostic factors in hematologic and solid malignancies. Thus, we sought to investigate if the preoperative absolute lymphocyte count (ALC) and absolute monocyte count (AMC) affects disease progression and survival after complete surgical resection of advanced malignant melanoma. Methods:We retrospectively reviewed records of 227 patients with resected advanced malignant melanoma (153 stage III and 74 stage IV) that were treated at the Mayo Clinic from 2000 to 2010. Survival analysis was performed using the Kaplan-Meier method, log-rank tests, and the Cox proportional hazards model for the univariate and multivariate analysis. Results:Surgically resected stage III melanoma patients with a preoperative AMC<0.6×109/L experienced a longer overall survival (OS) versus AMC≥0.6×109/L (median: 63.9 vs. 34.8 mo, respectively, P<0.008). Multivariate analysis showed AMC to be an independent predictor for OS in stage III patients. Stage IV resected melanoma patients with an ALC≥1.9×109/L experienced a superior median relapse-free survival (RFS) compared with patients with an ALC<1.9×109/L (median: 11.4 vs. 5.4 mo, respectively, P<0.006). Multivariate analysis showed ALC to be an independent predictor for RFS in stage IV patients. Conclusions:These data showed that in surgically resected stage III melanoma, preoperative AMC is an independent prognostic factor for OS. In contrast, a higher preoperative ALC is an independent prognostic for longer RFS in surgically resected stage IV melanoma.

Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis.

Pseudomyxoma peritonei (PMP) is a rare abdominal malignancy. We hypothesized that next-generation exomic sequencing would identify recurrent mutations that may have prognostic or therapeutic implications. Ten patients were selected on the basis of availability of tissue and adequate follow-up. They were treated at our institution between September 2002 and August 2004. Using next-generation exomic sequencing, we tested for mutations in 236 cancer-related genes in formalin-fixed paraffin-embedded slides. MCL1 amplification was additionally tested with immunohistochemical staining. Detectable mutations were found in 8 patients (80%). Seven patients harbored a KRAS mutation, most commonly involving codon 12. Four GNAS mutations (R201H/R201C substitutions) were also detected. MCL1 and JUN were concurrently amplified in three patients. One patient with MCL1 and JUN amplification had concurrent amplification of MYC and NFKBIA. ZNF703 was amplified in one patient. Patients with MCL1 amplification were also found to express MCL1 with immunohistochemistry, but MCL1 expression was also detected in some patients without amplification. To our knowledge, we are the first to report MCL1 and JUN coamplification in PMP. Expression of MCL1 may not be completely dependent on amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation.

Adjuvant GM-CSF improves survival in high-risk stage iiic melanoma: a single-center Study

Objectives:Stage III melanoma is associated with an increased risk of recurrence and death. Complete surgical resection remains the best chance for cure. Unfortunately, no adjuvant therapy has demonstrated a consistent improvement in melanoma-specific survival (MSS). We hypothesize that adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) may improve clinical outcomes. Patients and Methods:Retrospective cohort study of 317 surgically resected stage III melanoma patients managed with observation or adjuvant GM-CSF at a single institution from 2001 to 2010. Results:Of the 317 stage III patients, 165 (52%) were observed and 152 (48%) were treated with GM-CSF, with a median follow-up of 34 months. Patients treated with GM-CSF tended to be younger (P<0.0001), had more advanced stage disease (P=0.002), and were more likely to have had a recurrence before initiation of adjuvant therapy than the observation group (P<0.0001). Adjuvant GM-CSF seemed to be associated with improved MSS, but this did not reach statistical significance (P=0.08). Patients with stage IIIC melanoma derived a substantial benefit from adjuvant GM-CSF, with a 52% risk reduction in melanoma-specific death (hazard ratio 0.48; 95% confidence interval, 0.27-0.87; P=0.02). Conclusions:Despite selecting patients with more advanced stage and a higher incidence of regional relapse, adjuvant GM-CSF was associated with an improved MSS but not disease-free survival in patients with stage IIIC disease. In patients not otherwise eligible for clinical trials, adjuvant GM-CSF treatment is a reasonable option for individuals with resected high-risk melanoma.

Mayo Clinic Consensus Recommendations for the Depth of Excision in Primary Cutaneous Melanoma

Currently, no data from randomized controlled clinical trials are available to guide the depth of resection for intermediate-thickness primary cutaneous melanoma. Thus, we hypothesized that substantial variability exists in this aspect of surgical care. We have summarized the literature regarding depth of resection and report the results of our survey of surgeons who treat melanoma. Most of the 320 respondents resected down to, but did not include, the muscular fascia (extremity, 71%; trunk, 66%; and head and neck, 62%). However, significant variation exists. We identified variability in our own practice and have elected to standardize this common aspect of routine surgical care across our institution. In light of the lack of evidence to support resection of the deep muscular fascia, we have elected to preserve the muscular fascia as a matter of routine, except when a deep primary melanoma or thin subcutaneous tissue dictates otherwise.

Is there a role for endoscopic therapy as a definitive treatment for post-laparoscopic bile duct injuries?

BACKGROUND Excellent results of surgical reconstruction of major bile duct injuries (BDIs) have been well-documented. Reports of successful definitive management of central bile duct leakage and stenoses have been reported infrequently. The aim of this study was to assess treatment and outcomes for operative and endoscopic treatment of BDI after laparoscopic cholecystectomy (LC) and define the role of endoscopy in management. STUDY DESIGN All patients undergoing treatment for post-laparoscopic BDI from 1998 to 2007 at Mayo Clinic, Rochester, Minnesota were reviewed. Outcomes of surgical and endoscopic intervention were analyzed. RESULTS BDI was identified in 159 patients (mean age 51 years). Injury was recognized intraoperatively in 39 (25%) patients. Primary intervention was surgical in 59 (37%) and endoscopic in 100 (63%) patients. Class A BDIs (n = 77) were successfully treated endoscopically in 76 (99%) patients. Seven had class D BDIs; 4 were managed surgically, and 3 endoscopically. Of 66 patients with E1 to E4 BDI, 44 (67%) were initially managed surgically and 22 (33%) endoscopically. Thirteen of the latter 22 underwent sustained endoscopic therapy (median stent time 7 months), which was successful in 10 (77%). Four patients with E5 were managed surgically. Median follow-up was 45 months. Sixty-three patients underwent Roux-en-Y hepaticojejunostomy reconstruction at Mayo; 3 (5%) failed and required stenting. None required operative revision. CONCLUSIONS Endoscopic management of class A BDI has excellent outcomes. Although surgical management remains the preferred therapy, short-term endoscopic treatment for class E1 to E4 can optimize the patient and operative field for reconstruction. Prolonged stenting in select patients with E1 to E4 characterized by stenosis is successful in the majority.