Prognostic significance of tumor mitotic rate in T2 melanoma staged with sentinel lymphadenectomy.

BACKGROUND AND OBJECTIVES: Tumor mitotic rate (TMR) is an important prognostic variable for patients with thin melanoma. However it remains unclear what the significance of TMR is for more deeply invasive melanoma pathologically staged with a sentinel lymph node biopsy. We sought to determine the prognostic value of TMR in clinically node-negative T2 melanoma patients staged with sentinel lymphadenectomy. METHODS: A prospective IRB-approved database of cutaneous melanoma patients treated from 09/01/1997-03/01/2011 was used to identify patients with T2 melanoma staged with a SLN. Associations were evaluated using Fisher's Exact test, and Kaplan-Meier analysis. RESULTS: Three hundred thirteen T2 patients were included. 19% had ulceration, 11% a positive sentinel node (SLN), and 10% recurred. 44% of patients had TMR ≥ 1/mm(2). TMR ≥ 1/mm(2) did not predict SLN status. TMR ≥ 1/mm(2) was significantly associated with recurrence in SLN negative patients; only 3% of those with TMR < 1/mm(2) developed a recurrence compared to 16% of those with TMR ≥ 1/mm(2) (P < 0.0001). CONCLUSIONS: Although TMR ≥ 1/mm(2) is not associated with risk of SLN involvement in T2 melanoma, it is a significant risk factor for recurrence when SLN negative. As such, TMR could be used to stratify follow-up regimens in SLN negative T2 patients.

Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients.

OBJECTIVE AND BACKGROUND: Morbidity, mortality, and length of hospital stay after pancreaticoduodenectomy (PD) have significantly decreased over recent decades. Despite this progress, early readmission rates after PD have been reported as high as 50%. Few reports have delineated factors associated with readmission after PD. METHODS: The medical records of 6 high-volume institutions were reviewed for patients who underwent PD between 2005 and 2010. Data collection included patient characteristics, medical comorbidities, and perioperative factors. Analysis included readmissions up to 90 days after PD. RESULTS: A total of 1302 patients underwent PD across all institutions. The 30-day and 90-day readmission rates were 15% and 19%, respectively. The most common reasons for 30-day readmission included infectious complications (n = 65) and delayed gastric emptying (n = 29). The most common reasons for readmission after 90 days included wound infections and intra-abdominal abscess (n = 75) and failure to thrive (n = 38). On multivariate analysis, factors associated with higher readmission rates included a preoperative diagnosis of chronic pancreatitis, higher transfusion requirements, and postoperative complications including intra-abdominal abscess and pancreatic fistula (all P < 0.02). Factors not associated with higher readmission rates included advanced age, body mass index, cardiovascular/pulmonary comorbidities, diabetes, steroid use, Whipple type (standard vs pylorus preserving PD), preoperative endobiliary stenting, and vascular reconstruction. CONCLUSIONS: These multi-institutional data represent a large experience of PD without the biases typically of single center studies. Factors related to infection, nutritional status, and delayed gastric emptying were the most common reasons for readmission after PD. Postoperative complications including pancreatic fistula predicted higher rates of readmission.

Systematic review: surgery for patients with metastatic melanoma during active treatment with ipilimumab.

Studies of ipilimumab have shown improved overall survival in patients with metastatic cutaneous melanoma. As a result, use of ipilimumab in patients with Stage IV melanoma is rapidly increasing. Patients with Stage IV melanoma often require urgent operations for complications from metastases, but little is known about the safety of surgical intervention for patients receiving ipilimumab. We performed a systematic review of the literature using PubMed. Our search terms were melanoma and ipilimumab. We excluded foreign language articles, review articles, and those not addressing cutaneous melanoma. We identified 194 publications matching the search criteria. Only six of those met the inclusion criteria. In these six publications, seven patients who had undergone surgical intervention during treatment with ipilimumab were described. There were no documented surgical complications. We reviewed our institutional experience and identified an additional three patients. No postoperative complications could be attributed directly to ipilimumab. There are limited data on the safety of surgical intervention during treatment with ipilimumab. Preliminary reports suggest there is no reason to withhold or delay surgery for patients receiving ipilimumab therapy.

Routine restaging PET/CT and detection of initial recurrence in sentinel lymph node positive stage III melanoma.

BACKGROUND: Follow-up of patients with sentinel lymph node-positive stage III melanoma uses history, physical exam, and cross-sectional imaging. The aim of this study was to evaluate positron emission tomographic (PET)/computed tomographic (CT) scans in the detection of recurrence. METHODS: From 2003 to 2009, a single-institution prospective database of all cutaneous melanoma patients was used to identify sentinel lymph node-positive stage III patients with disease-free survival >1 year and 1 restaging PET/CT scan. RESULTS: Thirty-eight patients were identified, with a median follow-up period of 27.5 months. Seven (18%) developed recurrence (median time to recurrence, 25 months). Recurrences were detected as follows: 3 by patients, 1 by physician, 1 by PET/CT scan and lactate dehydrogenase, 1 by PET/CT scan, and 1 by brain magnetic resonance imaging. One hundred eight follow-up PET/CT scans were performed. Two of 38 patients had asymptomatic metastases detected by routine restaging PET/CT scan, and there were 9 scans with false-positive results. CONCLUSIONS: With short follow-up, the utility of routine PET/CT scans in identifying unsuspected recurrence in patients with sentinel lymph node-positive stage III melanoma appears minimal.

Perioperative blood transfusion is associated with decreased survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma: a multi-institutional study.

INTRODUCTION: In this multi-institutional study of patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, we sought to identify factors associated with perioperative transfusion requirement as well as the association between blood transfusion and perioperative and oncologic outcomes. METHODS: The surgical databases across six high-volume institutions were analyzed to identify patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma from 2005 to 2010. For statistical analyses, patients were then stratified by transfusion volume according to whether they received 0, 1-2, or >2 units of packed red blood cells. RESULTS: Among 697 patients identified, 42 % required blood transfusion. Twenty-three percent received 1-2 units, and 19 % received >2 units. Factors associated with an increased transfusion requirement included older age, heart disease, diabetes, longer operative time, higher blood loss, tumor size, and non-R0 margin status (all p < 0.05). The median disease-free survival (13.8 vs. 18.3 months, p = 0.02) and overall survival (14.0 vs. 21.0 months, p < 0.0001) durations of transfused patients were shorter than those of transfusion-free patients. Multivariate modeling identified intraoperative transfusion of >2 units (hazard ratio, 1.92, p = 0.009) and postoperative transfusions as independent factors associated with decreased disease-free survival. CONCLUSIONS: This multi-institutional study represents the largest series to date analyzing the effects of perioperative blood transfusion on patient outcomes following pancreaticoduodenectomy for pancreatic adenocarcinoma. While blood transfusion was not associated with increased rate of infectious complications, allogeneic blood transfusion did confer a negative impact on disease-free and overall survival.

Early recurrence in sentinel lymph node positive stage III melanoma patients.

Patients with sentinel lymph node (SLN) positive melanoma have a significant recurrence risk. We sought to examine variables associated with development of early recurrence. A prospective institutional review board-approved database of cutaneous melanoma patients treated from 2003 to 2010 was used to identify SLN positive stage III patients with 1 year of follow-up. The Kaplan-Meier method, and logistic regression were used to evaluate variables associated with early recurrence. Seventy-four patients were identified. Twenty-four (32%) had an early recurrence. Five variables were highly significantly associated with early recurrence: location of head/neck, Breslow depth greater than two, ulceration, number of lymph nodes positive ≥ 2, and largest lymph node metastasis > 1 mm. Using these five variables, a numerical risk score was created from 0 to 5 to determine if an early recurrence occurred as the number of risk factors increased. The proportion of patients with early recurrence increased in linear fashion with increasing risk score (P < 0.0001). These data suggest that SLN positive stage III melanoma patients have a significant risk of early recurrence, which is associated with several defined variables and increases with the number of risk factors present. These data may be useful in stratifying patients to level of recurrence risk and adjusting follow-up schedules.

Continuous detection and decoding of dexterous finger flexions with implantable myoelectric sensors.

A rhesus monkey was trained to perform individuated and combined finger flexions of the thumb, index, and middle finger. Nine implantable myoelectric sensors (IMES) were then surgically implanted into the finger muscles of the monkey's forearm, without any adverse effects over two years postimplantation. Using an inductive link, EMG was wirelessly recorded from the IMES as the monkey performed a finger flexion task. The EMG from the different IMES implants showed very little cross correlation. An offline parallel linear discriminant analysis (LDA) based algorithm was used to decode finger activity based on features extracted from continuously presented frames of recorded EMG. The offline parallel LDA was run on intraday sessions as well as on sessions where the algorithm was trained on one day and tested on following days. The performance of the algorithm was evaluated continuously by comparing classification output by the algorithm to the current state of the finger switches. The algorithm detected and classified seven different finger movements, including individual and combined finger flexions, and a no-movement state (chance performance = 12.5%) . When the algorithm was trained and tested on data collected the same day, the average performance was 43.8+/-3.6% n=10. When the training-testing separation period was five months, the average performance of the algorithm was 46.5+/-3.4% n=8. These results demonstrated that using EMG recorded and wirelessly transmitted by IMES offers a promising approach for providing intuitive, dexterous control of artificial limbs where human patients have sufficient, functional residual muscle following amputation.

Decoding individuated finger flexions with Implantable MyoElectric Sensors.

We trained a rhesus monkey to perform randomly cued, individuated finger flexions of the thumb, index, and middle finger. Nine Implantable MyoElectric Sensors (IMES) were then surgically implanted into the finger muscles of the monkey's forearm, without any observable adverse chronic effects. Using an inductive link, we wirelessly recorded EMG from the IMES as the monkey performed a finger flexion task. A principal components analysis (PCA) based algorithm was used to decode which finger switch was pressed based on the recorded EMG. This algorithm correctly decoded which finger was moved 89% of the time. These results demonstrate that IMES offer a safe and highly promising approach for providing intuitive, dexterous control of artificial limbs and hands after amputation.