Management of Pancreatic Neuroendocrine Tumors: Surgical Strategies and Controversies.

OBJECTIVE: Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors. METHODS: Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included PNETs, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed. RESULTS: Surgery continues to have a major role in the treatment of sporadic functional and nonfunctional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for non-functional PNETs < 2 cm in size. Surgical decision-making in multiple endocrine neoplasia type 1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients. CONCLUSIONS: Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery is essential to manage these patients.

Identification and Resection of Clipped Node Decreases the False-negative Rate of Sentinel Lymph Node Surgery in Patients Presenting With Node-positive Breast Cancer (T0-T4, N1-N2) Who Receive Neoadjuvant Chemotherapy: Results From ACOSOG Z1071 (Alliance).

BACKGROUND: The American College of Surgeons Oncology Group Z1071 trial reported a false-negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery. METHODS: Z1071 was a multi-institutional trial wherein women with clinical T0-T4,N1-N2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated. RESULTS: A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (confidence interval [CI]: 1.9%-16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI: 5.4%-41.9%). In cases without a clip placed (n = 355) and in those where clipped node location was not confirmed at surgery (n = 29), the FNR was 13.4% and 14.3%, respectively. CONCLUSIONS: Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when conducting SLN surgery in this setting.

Merkel cell carcinoma: high recurrence rate despite aggressive treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cancer of the skin whose incidence has been increasing. The objective of the study was to evaluate current treatment modalities, including sentinel lymph node (SLN) biopsy and outcomes and identify prognostic factors in patients with MCC. METHODS: A retrospective chart review of patients with MCC. Clinical, pathologic, treatment characteristics, disease status, and survival were collected. All slides were reviewed by a single pathologist, and additional pathologic elements were evaluated for prognosis. RESULTS: Twenty-six patients were identified in the study period. All patients were Caucasian with an average age of 71.3 y. Twenty-one patients had tumors in sun-exposed locations, and 13 had a prior history of skin cancer. All nonmetastatic patients underwent wide excision. SLN biopsy was successful in 19 patients. The SLN was positive in 21% of patients. Radiation therapy was used in 13 patients. Average follow-up was 26 mo, and median survival was 29 mo. Recurrence occurred in eight patients: four locoregional, two distant, one combined, and one unknown. Recurrence occurred in five patients with stage I disease. Five patients with negative SLN later developed recurrence. The presence of metastasis to the nodes was significant for recurrence. No other pathologic factor was found to have prognostic significance. CONCLUSIONS: Despite aggressive surgical and radiation treatment, MCC has a high rate of locoregional recurrence, even in early stage disease. SNLB is useful for the staging and management of patients. Further research is needed to identify better prognostic markers.

A Rare Adrenal Incidentaloma That Mimics Adrenocortical Carcinoma.

OBJECTIVE: We present a case of an adrenal hemangioma, an uncommon cause of an adrenal mass, and review the clinical presentation, work-up, and management of adrenal incidentalomas. BACKGROUND: A 64-year-old male was found to have a right adrenal incidentaloma during work-up for elevated liver transaminase levels, later found to be from hepatitis C. The mass was suspicious for adrenocortical carcinoma on CT imaging. Biochemical evaluation revealed no evidence of function. He underwent an open right adrenalectomy. The mass was found to be an adrenal hemangioma on histopathologic analysis. METHODS: This is a case report with pertinent review of the diagnosis and management of adrenal incidentalomas. RESULTS: Adrenal hemangiomas are rare, benign, nonfunctional tumors typically found during imaging for other reasons. As illustrated by this case, they appear similar to adrenocortical carcinoma on CT imaging. The diagnosis is usually not made prior to surgical resection. CONCLUSION: Adrenal hemangioma is a rare nonfunctional adrenal incidentaloma that displays atypical features on CT imaging. The suspicion for adrenocortical carcinoma usually prompts adrenalectomy.

Pump removal in infected patients with hepatic chemotherapy pumps: when is it necessary?

Hepatic chemotherapy pumps have been shown to be an effective and well-tolerated treatment for metastatic colorectal cancer confined to the liver. The importance of completing chemotherapy in long-term outcome makes it desirable to salvage hepatic pumps where possible. Concerns of persistent and systemic infection have resulted in premature removal of pumps in patients with infection. We report our experience in this clinical scenario. We placed 75 hepatic chemotherapy pumps from January 1998 to August 2005 for treatment of colorectal liver metastases. Information was collected on the patients' courses of treatment, complications, and demographics via chart review. The rate of infection was 22.7% (n = 17), including eight infections localized to the abdomen (entailing five wound infections, three hepatic abscesses, and two pump pocket infections). Of these, two pumps had to be removed because of pump pocket infection, and these patients received more cycles of chemotherapy compared with the four removed for noninfectious complications (12.3 vs 3.2, P = 0.0349). Time to infection was found to be significantly higher in these patients (12.5 months) than in the patients with infections overall (4.87 months, P = 0.029), and age was found to be lower (42.5 vs 57.6 years, P = 0.0068).

Ultrasound-guided breast biopsy for surgical residents: evaluation of a phantom model.

BACKGROUND: Ultrasound is increasingly used by surgeons for evaluation of breast lesions. While surgical residents have sufficient exposure to breast surgery, many lack exposure to office-based procedures, such as ultrasound-guided breast biopsy. A phantom model was created to teach surgical residents basic breast ultrasound and biopsy skills and to evaluate the resident's response when incorporated into the curriculum. METHODS: The model was created using a pork roast and 10 variably-sized pimento olives. Twenty-four surgical residents were given a brief introduction to breast ultrasound followed by up to 5 minutes to ultrasound the model and note the embedded lesions. The number and location of lesions found and the time spent per resident were recorded. Residents were then introduced to the vacuum-assisted core biopsy system and observed performing ultrasound-guided biopsies. Pre- and postsession evaluations were completed by all residents. Scatterplot regression models were used for data analysis. RESULTS: Most residents had previous ultrasound instruction. The intermediate level residents (postgraduate year [PGY]2 and 3) found the most lesions in the shortest time, missing on average 1.125 lesions in 3:09 minutes. Time spent did not correlate with number missed or previous ultrasound experience. Over 50% of residents sampled the center of the lesion on their first biopsy attempt, with no correlation to PGY or ultrasound experience. All residents rated this experience good to excellent, and 67% believed their ultrasound skills were improved. Ninety-five percent of residents felt the model was fairly realistic and 95% would like to have more experiences like this in the curriculum. The residents surveyed thought the curriculum would be best suited to a PGY2 experience. CONCLUSIONS: The phantom breast is a realistic and valuable teaching model for breast ultrasound. Further evaluation regarding skill retention is needed.

Serum proteomic biomarker discovery reflective of stage and obesity in breast cancer patients.

BACKGROUND: Currently no standardized blood test exists for breast cancer screening or staging purposes. The goals of this study were to use proteomic mass spectrometry approaches for profiling, fractionation, and identification of serum proteins from breast cancer patients for discovery of new biomarkers of stage and nodal status. STUDY DESIGN: Samples from 150 patients were collected preoperatively for patients undergoing breast biopsy. Serum was processed using weak cation exchange (WCX) fractionation and analyzed with matrix-assisted laser desorption ionization time of flight mass spectrometry. Spectra were processed and group profiles, peak statistics, and cross-validation scores were determined using a k-nearest neighbor genetic algorithm. Pools of subgroups based on stage, race, and obesity were processed with WCX fractionation followed by trypsin digestion. Differentially expressed proteins and peptides were identified by tandem mass spectrometry. RESULTS: Matrix-assisted laser desorption ionization time of flight proteomic profiling using WCX capture of serum proteins resulted in correct cancer stage classifications ranging from 72% to 84%. Nodal status was classified correctly with 88% cross-validation scores. Levels of endogenous low mass peptide fragments derived from kininogen, fibrinogen, plasminogen, and inter-alpha-trypsin inhibitor heavy chain 4 protein were increased in cancer stage III and stage IV samples. Adding trypsin digestions with WCX capture indicated increased levels of alpha-2-HS-glycoprotein, prothrombin, and serum amyloid A in stage IV samples. Obesity, but not race, was a factor in the relative levels of detected proteins/peptides. CONCLUSIONS: WCX fractionation alone or with trypsin digestion of serum suggest it can be possible to use a panel of proteins to predict breast cancer stage and nodal status. Additional study is required on the role of inflammatory molecules in breast cancer development.

Radiofrequency ablation of liver metastases from colorectal carcinoma.

BACKGROUND: Most patients with colorectal carcinoma will develop liver metastases. Radiofrequency ablation (RFA) has been utilized in metastatic CRC to help improve the survival gap between resectable and unresectable tumor. METHODS: The current use of RFA in selected patient populations is reviewed. RESULTS: RFA provides a survival benefit in patients with unresectable hepatic metastases from CRC compared with chemotherapy alone. It offers effective local tumor destruction in appropriately selected lesions and minimizes the morbidity and mortality of an open resection. Common complications are abdominal bleeding (1.6%), abdominal infection (1.1%), and injury to the biliary tree (1.0%). Mortality ranges from 0% to 0.5%. CONCLUSIONS: Trials are underway to compare chemotherapy plus local ablation to chemotherapy alone. RFA is a tool that should be utilized by experienced individuals to achieve optimal oncologic outcomes.

Late renal allograft rupture in a patient with small vessel vasculitis following discontinuation of immunosuppression.

We report the case of a 21-year-old man with antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis who experienced spontaneous renal allograft rupture 21 months after engraftment. Because of chronic allograft nephropathy, the patient's immunosuppressive regimen had been discontinued approximately 3 weeks prior to his presentation with abdominal pain and evidence of internal hemorrhage. He was emergently taken to the operating room, where a ruptured allograft was found and transplant nephrectomy was performed. Postoperatively, the cause of rupture was determined to have been acute cellular rejection. This case may be the longest interval reported between renal transplant and spontaneous allograft rupture.