Prognostic Factors in Typical and Atypical Pulmonary Carcinoids.

BACKGROUND: Typical and atypical carcinoids represent approximately 2% of all lung tumors. Survival of patients with typical bronchial carcinoids, unlike the survival of patients with most lung tumors, is generally long but dependent on stage. We report the findings of the Ochsner Medical Center/Louisiana State University (LSU) Health Sciences Center neuroendocrine tumor (NET) program. METHODS: A database with all patients seen at the Ochsner Medical Center/LSU NET program was queried for patients with bronchopulmonary NET. We included patients who had confirmed pathologic bronchopulmonary carcinoid and who had at least 1 clinic visit. Patients with large or small cell NETs or diffuse idiopathic pulmonary neuroendocrine cell hyperplasia were excluded. RESULTS: A total of 169 patients seen from January 1996 to March 2015 met the inclusion criteria. The mean age at diagnosis was 53 years. Of the tumors, 51% percent (86/169) were well-differentiated, 12% (21/169) were moderately differentiated, and 85% and 53% were positive on positron emission tomography and octreotide scanning, respectively. The 5- and 10-year survival rates were 88% and 81% for well-differentiated tumors and 80% and 42% for moderately differentiated tumors, respectively. The 10-year survival rates stratified by Ki-67 index ranges 0-2%, >2%-10%, and >10% were 90%, 72%, and 44%, respectively (P<0.05). CONCLUSION: Overall, patients with bronchial carcinoids have long 5- and 10-year survival rates. We found significant survival differences between nodal status, differentiation status, and carcinoid phenotype. Interestingly, the difference in survival stratified by Ki-67 indices was statistically significant despite its absence in the World Health Organization grading system. As with gastroenteropancreatic NETs, Ki-67 index could become a valuable prognostic indicator for bronchial carcinoids.

Neuroendocrine tumors (NETs) of unknown primary: is early surgical exploration and aggressive debulking justifiable?

BACKGROUND: Neuroendocrine tumors (NETs) are rare tumors that often present with vague symptoms. Identification and localization of the primary NET can be challenging and the true incidence remains unclear. These patients have been thought to have a poor prognosis compared to those patients with a known primary. Therefore, traditionally the treatments for patients with unknown primaries have been passive and directed towards symptom control and/or cytoreduction of metastatic disease. We hypothesized that NET of unknown primary are predominantly low-grade and easily located surgically and therefore are amendable to surgical debulking and cytoreduction, which will likely increase survival in these patients. METHODS: The charts for all 342 surgical patients, seen in our clinic at Ochsner-Kenner between 1/2009 and 9/2012 were retrospectively reviewed to determine which patients had a pre-operative diagnosis of a "NET with unknown primary". Twenty-two patients (6.4%) were identified. For these patients, the rate of successful surgical exploration in which a primary site was identified was recorded. Survival for these "unknown primary" patients were compared to a large similar group of NET patients from a recent study collected from this same Ochsner clinic group. RESULTS: Twenty-two (22/342, 6.4%) NET patients with a pre-operative diagnosis of an unknown primary were explored and cytoreduced. The primary tumor site was identified in all 22 patients (100%). The primary sites identified for these patients were 19 small intestines (86.4%) and 3 pancreatic (13.6%). All 22 patients had low-grade tumors and all were still alive as of 9/2012, not allowing for a survival curve to be generated. CONCLUSIONS: Unknown primary NETs are not associated with a poor prognosis as previously reported. Timely surgical exploration and debulking always results in the identification of the primary and a maximum cytoreduction. Early surgical exploration with aggressive debulking is indicated for the treatment of these patients, as for the known counterpart.

A single institution's experience with surgical cytoreduction of stage IV, well-differentiated, small bowel neuroendocrine tumors.

BACKGROUND: Well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract are rare, slow-growing neoplasms. Clinical outcomes in a group of stage IV, well-differentiated patients with NETs with small bowel primaries undergoing cytoreductive surgery and multidisciplinary management at a single center were evaluated. STUDY DESIGN: The charts of 189 consecutive patients who underwent surgical cytoreduction for their small bowel NETs were reviewed. Information on the extent of disease, complications, and Kaplan-Meier survival were collected from the patient records. RESULTS: A total of 189 patients underwent 229 cytoreductive operations. Ten percent of patients required an intraoperative blood transfusion and 3% (6 of 229) had other intraoperative complications. For all 229 procedures performed, mean (± SD) stay in the ICU was 4 ± 3 days and in the hospital was 9 ± 10 days. Before discharge, 51% of patients had no postoperative complications and 39% of patients had only minor complications. In a 30-day follow-up period from discharge, 85% of patients had no additional complications and 13% had only minor complications. The 30-day postoperative death rate was 3% (5 of 189). Mean survival from histologic diagnosis of NET was 236 months. The 5-, 10-, and 20-year Kaplan-Meier survival rates from diagnosis were 87%, 77%, and 41%, respectively. CONCLUSIONS: Cytoreductive surgery in patients with well-differentiated midgut NETs has low mortality and complication rates and is associated with prolonged survival. We believe that cytoreductive surgery is a key component in the care of patients with NETs.

An extended phase II trial of iodine-125 methylene blue for sentinel lymph node identification in women with breast cancer.

BACKGROUND: The aim of this study was to determine if an intraoperative injection of iodine-125-labeled methylene blue ((125)I-MB) is a sensitive and effective method for detecting SLNs in women with breast cancer. STUDY DESIGN: Sixty-two women were enrolled in an extended phase II trial using (125)I-MB to guide SLNB. All patients were anesthetized and then injected subcutaneously with 1 mCi (125)I-MB in the outer quadrant of the areola. RESULTS: Radioactivity was detected in the axilla within 3 to 5 minutes. Fifty-eight of 62 (94%) patients had SLNs detected during their procedure. Mean (±SD) number of SLNs per patient was 1.8 ± 1.3 (range 0 to 6). A total of 112 nodes were dissected from 58 women; 110 of these nodes were considered sentinel. One hundred and eight (98%) nodes were hot, 98 (89%) nodes were blue, and 96 (87%) nodes were both hot and blue. Two women had complications; 1 had superficial skin staining and 1 had a superficial skin slough. Both healed uneventfully. No allergic reactions were observed. No radioactive uptake in the thyroid was seen. CONCLUSIONS: Iodine-125-labeled methylene blue can be mixed and administered in the operating room, improving hospital efficiency. Patient satisfaction is higher with (125)I-MB than with the technetium 99m sulfur colloid procedure because (125)I-MB does not produce localized burning and other adverse reactions associated with the traditional method, and 125I-MB is administered with the patient under anesthesia. Iodine-125 emits a lower-energy gamma ray than technetium 99m, lowering the surgeon's radiation exposure. Iodine-125-labeled methylene blue SLN identification is safe, cost effective, and produces equivalent outcomes compared with the traditional technique, making it an attractive alternative.

Neurokinin A levels predict survival in patients with stage IV well differentiated small bowel neuroendocrine neoplasms.

BACKGROUND: Recent European investigations have shown that persistently elevated (>50 pg/mL) plasma neurokinin A levels are associated with poor short-term survival in patients with midgut neuroendocrine neoplasms. We hypothesized that American patients with persistently elevated plasma neurokinin A levels (>50 pg/mL) will also have a poor short-term survival. METHODS: Serial plasma neurokinin A levels were collected from the charts of 180 patients with metastatic midgut neuroendocrine neoplasms. Patients were grouped according to their plasma neurokinin A values, and survival rates were calculated. Group 1 had plasma neurokinin A levels <50 pg/mL. Group 2 at one point had plasma neurokinin A levels >50 pg/mL, but are currently <50 pg/mL. Group 3 had plasma neurokinin A values consistently >50 pg/mL. RESULTS: Group 1 patients (n = 143) have not reached their median survival and have a 24-month survival of 93%. Thirteen of 14 (93%) group 2 patients are currently alive. Group 3 patients (n = 23) had a median survival of 20 months and a 24-month survival of 48%. CONCLUSION: Patients with midgut neuroendocrine neoplasms who have serial plasma neurokinin A levels <50 pg/mL have an excellent short-term prognosis, while patients with plasma neurokinin A levels >50 pg/mL have a poor short-term prognosis.

A prospective evaluation of the effect of chronic proton pump inhibitor use on plasma biomarker levels in humans.

OBJECTIVE: Proton pump inhibitors (PPIs) are used primarily to treat gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely used biomarker for the diagnosis and follow-up for gut-based neuroendocrine tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin levels. METHODS: Thirty patients who used PPIs for 6 months or more (mean ± SD duration, 3.1 ± 2.5 years) and a separate control group of 30 patients who never used antacid medications were prospectively evaluated with plasma gastrin, CGA, and pancreastatin determinations. RESULTS: Chronic PPI use resulted in significant increases in CGA (15.1 ± 11 vs 131 ± 207 ng/mL; P = 0.005) and significant increases in gastrin (34.8 ± 22.3 vs 167.8 ± 136.2 pg/mL; P = 0.001) compared to controls. In contrast, pancreastatin level in nonusers and chronic PPI users were identical (81.6 ± 36.4 vs 89.4 ± 43.4 pg/mL; P = 0.46). CONCLUSIONS: Pancreastatin levels do not change with chronic PPI use and normal pancreastatin levels may be used to distinguish between drug-induced changes in biomarkers and tumor-related increases in circulating biomarkers.