Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients?

BACKGROUND: Midgut neuroendocrine tumor (NET) patients are often diagnosed at advanced stages with extensive mesenteric nodal and hepatic metastasis. The only potentially curative treatment is surgical tumor eradication. Despite an aggressive resection, macro and microscopic residual disease still may remain in the resection bed. We hypothesize that the application of 5-fluorouracil (5-FU) within the tumor bed will help eliminate microscopic residual disease. METHODS: Records of 189 patients who underwent extensive cytoreductive surgeries during 2003-2012 for advanced, midgut NETs with extensive mesenteric lymphadenopathy were reviewed. Eighty-six patients (46%) who had 5-FU saturated gel foam strips secured into their mesenteric resection sites served as the study group and a matching 103 patients (54%) who did not have such an intra-operative chemotherapy served as controls. Survival from the time of diagnosis and post-operative complications between the two groups were compared. RESULTS: Mortality rates at 30, 60 and 90 days post-operatively were 4%, 0%, 0% versus 2%, 0%, 2% for study and control groups, respectively. Major complications (Grades III & IV) at the same intervals were 0, 0, 1 versus 2, 3, 2 for study and control groups, respectively. Median survival was 236 months versus 148 months for the study and control groups, respectively 24 (P=0.15). CONCLUSIONS: Intraoperative tumor resection bed chemotherapy is a safe adjuvant without discernible toxicity. This procedure may provide survival benefits to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery. Further study in prospective trials must be conducted to determine definitive benefit to the NET patient.

Plasma Neurokinin A Levels Predict Survival in Well-Differentiated Neuroendocrine Tumors of the Small Bowel.

OBJECTIVES: Elevated neurokinin A (NKA) levels are associated with poor prognosis in patients with small bowel neuroendocrine tumors. We hypothesized that patients with NKA levels that remain elevated despite treatment with surgical cytoreduction have a poor prognosis. METHODS: Patients diagnosed with small bowel neuroendocrine tumors who underwent surgical cytoreduction at our institution were identified. Demographics, histopathologic characteristics, and biochemical data were collected. Patients were grouped by the trend of their NKA levels (group 1, continuously normal; group 2, transiently elevated but normalized after therapy; group 3, remained elevated despite therapy). Survival rates were calculated from the date of the patient's first NKA level. RESULTS: Serial NKA values after surgical cytoreduction were monitored in 267 patients. Kaplan-Meier 2-year, 5-year, and 10-year survival rates were as follows: group 1 (n = 157), 97%, 89%, and 62%; group 2 (n = 78), 99%, 90%, and 78%; and group 3 (n = 32), 88%, 69%, and 0%. Survival rates were statistically significant between groups 1 and 3 and between groups 2 and 3 (P < 0.01). CONCLUSIONS: Serial monitoring of plasma NKA levels is useful in identifying patients who have a poor prognosis. Elevated NKA levels can indicate the need for immediate therapeutic intervention.

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.

The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society.

Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.

Aggressive Surgical Approach to the Management of Neuroendocrine Tumors: A Report of 1,000 Surgical Cytoreductions by a Single Institution.

BACKGROUND: Neuroendocrine tumors (NETs) are rare neoplasms. Our group has treated more than 2,000 NET patients and has performed more than 1,000 surgical cytoreductive procedures. STUDY DESIGN: Records of 834 NET patients who underwent surgical cytoreduction at our institution were reviewed. Demographic information, intraoperative findings, extent of disease, complications, and survival rates were calculated. RESULTS: Eight hundred patients underwent 1,001 cytoreductive operations. Sixty-five percent had small bowel primaries. One hundred and thirty-eight patients presented with an unknown primary site, which was localized intraoperatively in 89% of these cases. The intraoperative complication rate was 9%. The incidence of intraoperative carcinoid crisis was 1%. Mean ± SD operative time was 368 ± 146 minutes. Mean ± SD hospital stay was 9 ± 10 days. Minor postoperative complications occurred after 43% of procedures and major postoperative complications were noted after 19% of procedures. The 30-day postoperative mortality rate was 2%. Median overall survival (OS) for patients with pancreatic NETs was 124 months. The 5-, 10-, and 20-year OS rates for patients with pancreatic NETs were 67%, 51%, and 36%, respectively. The life expectancy difference (between OS and actuarial survival) after surgical cytoreduction for patients with pancreatic NETs was 16.6 years. Median OS for patients with small bowel NETs was 161 months. The 5-, 10-, and 20-year OS rates for patients with small bowel NETs were 84%, 67% and 31%, respectively. The life expectancy difference after surgical cytoreduction for patients with small bowel NETs was 11.7 years. CONCLUSIONS: Surgical cytoreduction in NET patients has low morbidity and mortality rates and results in prolonged survival. We believe that surgical cytoreduction should play a major role in the care of patients with NETs.

Development of effective prophylaxis against intraoperative carcinoid crisis.

STUDY OBJECTIVE: The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. DESIGN: A retrospective study was approved by the institutional review boards at Ochsner Medical Center-Kenner and Louisiana State University Health Sciences Center. SETTING: Ochsner Medical Center-Kenner operating room and multispecialty NET clinic. PATIENTS: One hundred fifty consecutive patients who underwent a total of 179 cytoreductive surgeries for stage IV, small bowel NETs. INTERVENTIONS: All patients received a 500-µg/h infusion of octreotide acetate preoperatively, intraoperatively, and postoperatively. MEASUREMENTS: Anesthesia and surgical records were reviewed. Carcinoid crisis was defined as a systolic blood pressure of less than 80mm Hg for greater than 10minutes. Patients who experienced intraoperative hypertension or hypotension, profound tachycardia, or a "crisis" according to the operative note were also reviewed. MAIN RESULTS: One hundred sixty-nine (169/179; 94%) patients had normal anesthesia courses. The medical records of 10 patients were further investigated for a potential intraoperative crisis using the aforementioned criteria. Upon review, 6 patients were determined to have had a crisis. The final incidence of intraoperative crisis was 3.4% (6/179). CONCLUSIONS: A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis. We believe that the low cost and excellent safety profile of octreotide warrant the use of this therapy during extensive surgical procedures for midgut and foregut NETs.

The Role of Capecitabine/Temozolomide in Metastatic Neuroendocrine Tumors.

BACKGROUND: Neuroendocrine tumors (NETs) are commonly treated with multimodality therapy. The combination of capecitabine and temozolomide (CAPTEM) has been suggested as a treatment option for patients with metastatic NETs. We present our experience with CAPTEM. METHODS: Data on NET patients who were placed on CAPTEM and received at least one cycle were obtained from a Velos eResearch database. Response rate was calculated by RECIST 1.1. Overall survival and progression-free survival (PFS) were calculated by the Kaplan-Meier survival method. RESULTS: A total of 29 patients (17 male and 12 female) were included. Median age at CAPTEM initiation was 58 years (range: 26-77). Primary tumors included 9 small bowel (31%), 15 pancreas (52%), 3 lung (10%), and 2 rectum (7%). Median number of CAPTEM cycles was 8 (range: 1-55). Partial response occurred in 5 patients (5 of 29, 17%); 14 patients (14 of 29, 48%) had stable disease, and 10 patients (10 of 29, 34%) had progressive disease. A total of 3 (20%) and 5 (33%) pancreatic NETs experienced partial response and stable disease, respectively. A total of 2 (14%) and 9 (64%) nonpancreatic NETs experienced partial response and stable disease, respectively. Partial response was noted in 1 patient (13%) and stable disease in 5 patients (63%) with Ki-67 values of less than 2%. In patients with Ki-67 values of 2%-20%, partial response was noted in 3 (19%) and stable disease in 8 (50%). Partial response and stable disease were noted in 1 patient each (20%) with Ki-67 values greater than 20%. Median PFS was 12 months. Adverse reactions caused dose reductions in 24% of patients. CONCLUSION: Although adverse reactions were experienced, most patients tolerated this regimen. CAPTEM should be considered as a reasonable treatment option for metastatic NET patients. IMPLICATIONS FOR PRACTICE: The role of chemotherapy in neuroendocrine tumors has evolved in recent years. The results of this study suggest that the combination of capecitabine and temozolomide provides an adequate treatment option and may prolong survival in patients with a wide variety of metastatic neuroendocrine tumors. Although prospective data are needed, this research adds to the abundance of retrospective experience with this combination that appears to show that capecitabine and temozolomide could potentially be an option for patients with advanced neuroendocrine tumors who have progressed on standard treatment.

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.

Obturator Canal Lymph Node Metastasis from Rectal Carcinoid Tumors: Total Mesorectal Excision May Be Insufficient.

BACKGROUND: Optimal surgical treatment for small early rectal carcinoids is controversial. Large tumors (greater than 2 cm) and those with imaging evidence of lymph node metastasis are generally treated by low anterior resection (LAR) with total mesorectal excision (TME). We first observed and reported that midgut carcinoid with extensive mesenteric lymphadenopathy often develops alternated lymphatic drainage pathways. We hypothesize that rectal carcinoids have the same potential to develop alternated lymphatic pathways outside the mesorectal envelope, which allows tumor deposits to be missed by traditional TME. METHODS: Twenty-two consecutive rectal carcinoid surgical patient charts were reviewed to determine if alternated lymphatic drainage occurred and resulted in extra-mesorectal metastasis. We attempted to identify any risk factor(s) that may lead to developing such alternated lymphatic drainage pathways. RESULTS: Thirteen patients underwent initial LAR with TME (13/22, 59 %) and nine underwent a staged debulking for locoregional residual disease or regional/distant metastasis after previous resection (9/22, 41 %). Fourteen (14/22, 64 %) underwent radio-guided surgery in attempt to achieve a higher level of pelvic/distant metastatic disease detection and debulking. Six patients (6/22, 27 %) had obturator canal lymph node metastases confirmed histologically. CONCLUSIONS: Based on our study, at least 27 % of rectal carcinoid patients may have extra-mesorectal metastasis that would be missed by the traditional TME. Radio-guided surgery can identify and remove such metastasis. The effect of having such extra-mesorectal metastasis and its surgical removal on long-term survival has yet to be determined.

Elevated Plasma Pancreastatin, but Not Chromogranin A, Predicts Survival in Neuroendocrine Tumors of the Duodenum.

BACKGROUND: Neuroendocrine tumors (NETs) of the duodenum are rare, heterogeneous, and often indolent neoplasms. We hypothesized that elevated pancreastatin levels are an indicator of a poor prognosis in well-differentiated duodenal NETs. STUDY DESIGN: Data from patients diagnosed with a primary duodenal NET were analyzed. Patients that underwent esophogogastroduodenoscopy, endoscopic ultrasound, or exploratory surgery to localize their neoplasm and whose tumors were confirmed histologically were included. RESULTS: Eighty-four patients were diagnosed with duodenal NETs from January 1991 to January 2014. Seventy-five percent and 21% of patients had their tumor localized by esophogogastroduodenoscopy and endoscopic ultrasound, respectively. The remaining 4% were localized during exploratory surgery. The 5-year Kaplan-Meier survival rate for the entire cohort (N = 84) was 80%. Survival sorted by normal vs abnormal pancreastatin level was statistically significant (p < 0.0001). Five-year survival rates were 94% and 37% for normal and abnormal pancreastatin, respectively. In contrast, survival sorted by normal vs abnormal plasma chromogranin A level was not statistically significant (p = 0.24). CONCLUSIONS: Patients with primary duodenal NETs have high 5-year survival rates. Serial monitoring of plasma pancreastatin levels can identify patients who have a poor prognosis.

Adjuvant intraoperative post-dissectional tumor bed chemotherapy-A novel approach in treating midgut neuroendocrine tumors.

BACKGROUND: Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. Even with skillful surgical dissection, macro and microscopic residual disease at the dissection site remains a possibility. We hypothesize these potential tumor residuals in mesenteric lymph node dissection beds can be eliminated safely by a local application of 5-fluorouracil (5-FU). We describe a novel technique invented by the author to treat these micro and macro residuals. METHODS: Retrospectively, charts of 62 consecutive midgut NET patients with boggy mesenteric lymphadenopathy who underwent cytoreductive debulking surgeries from 1/2007 to 12/2009 were reviewed. A total of 32 patients received an intraoperative application of 5-FU saturated gelfoam strips secured into the mesenteric defect following the extensive lymphadenectomy. A total of 30 untreated patients served as a control. RESULTS: The 5-year survival after cytoreductive surgeries was 22/32 (68.8%) for the treated group, vs. 20/30 (66.7%) for the control. Six patients (6/32, 18.8%) among the study group required additional debulking surgeries, vs. 16 patients (16/30, 53.3%) in the control group. Upon reoperation, loco-regional recurrence was noted in 9 of the 16 patients (56.3%) in the control group, vs. only 2/6 (33.3%) of treated patients. Overall, local recurrence rate is 6.25% (2/32) in the treated group vs. 30% (9/30) in the control group. Post-op complication rates are similar in the two arms. CONCLUSIONS: Intraoperative application of chemotherapy is a safe and effective adjuvant to reduce local recurrence and the need of reoperation by the tumoricidal or tumorstatic effects of 5-FU on any potential microscopic residual disease after extensive cytoreductive surgeries in advanced stage NET patients with mesenteric lymph node metastasis. It provides patients with sustained, slow releasing, high dose of 5-FU within the surgical bed with a negligible side effect profile. Further studies are required to evaluate its effect on long term survival.

Reappraisal of lymphatic mapping for midgut neuroendocrine patients undergoing cytoreductive surgery.

BACKGROUND: We previously reported that midgut neuroendocrine tumors (NETs) often develop alternative lymphatic drainage owing to lymphatic obstructions from extensive mesenteric lymphadenopathy, making intraoperative lymphatic mapping mandatory. We hypothesize that this innovative approach needs a longer term validation. METHODS: We updated our results by reviewing 303 patients who underwent cytoreduction from November 2006 to October 2011. Of these patients, 112 had lymphatic mappings and 98 were for midgut NET primaries. Among them, 77 mappings were for the initial cytoreduction and 35 were for reexploration and further cytoreduction. The operative findings, pathology reports, and long-term surgical outcomes were reviewed. RESULTS: Lymphatic mapping changed traditional resection margins in 92% of patients. Of the 35 patients who underwent reexploration without initial mapping, 19 (54%) showed a recurrence at or near the anastomotic sites. In contrast, none of the 112 mapped patients had shown signs of recurrence in a 1- to 5-year follow-up. Additionally, 20 of 45 ileocecal valves (44.4%) were spared in patients whose tumors were at the terminal ileum that, traditionally, would call for a right hemicolectomy. CONCLUSION: With a longer follow-up, lymphatic mapping has proven to be a safe and effective way to prevent local recurrences and preserve the ileocecal valve for selected patients.

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.

Cocoon formation in patients with midgut neuroendocrine tumors: a rare and unrecognized final pathway.

OBJECTIVES: Neuroendocrine tumors (NETs) are relatively rare with an indolent nature. As a result, treatment is often delayed and passive. The most commonly recognized disease progression leading to death is from the sequelae of bowel obstruction, ischemia, or liver failure secondary to liver metastasis. We recently recognized a rare cocoon-like formation in patients with metastatic gastroenteropancreatic NETs and hypothesize that this may be a distinct, final pathway for these patients. METHODS: Ten patients with stage IV gastroenteropancreatic NETs, seen at our center between October 2008 and November 2011, who developed a cocoon were identified. Patient's charts, operative reports, pathology, and tumor markers were reviewed. RESULTS: No discernable predictors were identified as precursors to this condition. One patient survived 13 months after cocoon diagnosis, and the remaining 9 patients were all deceased within 5 months. Surgical treatment was attempted in 6 patients and was only partially successful in 1 patient who had the earliest stage of cocoon formation (type 1). CONCLUSIONS: Cocoon-like formations in patients with stage IV gastroenteropancreatic NETs is rare and may be a terminal disease progression that has not been previously recognized. The best treatment option remains unknown. Surgical treatment is not advisable, with the exception of type 1 abdominal cocoons.

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.

Cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors: true incidence and management.

BACKGROUND: The incidence, clinical importance, and optimal management of cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors (NETS) are largely unknown. Historically, cervical nodes have been regarded as asymptomatic and ignored. We hypothesized that these lesions have clinical implications and should be removed surgically. STUDY DESIGN: Consecutive (111)In pentetreotide scans (OctreoScan) performed at our institution from May 2008 to October 2010 were reviewed to determine the incidence of cervical and upper mediastinal lymph node metastases among patients with gastrointestinal and pancreatic NETs. The charts of surgically treated patients were reviewed to evaluate the clinical importance of these metastases and the subsequent outcomes of their surgical treatment. RESULTS: A total of 161 NET patients presented with positive OctreoScans. Fourteen patients (8.7%) scanned positive for cervical and upper mediastinal lymph node metastasis. Nine patients underwent surgical exploration; 8 had successful removal of their metastatic nodes. Seven had clinical symptoms that resolved after surgery. CONCLUSIONS: Cervical and upper mediastinal lymph node metastases from gastrointestinal and pancreatic NETs were seen in up to 8.7% of patients. In the past, these metastases were assumed to be insignificant and ignored. Our study clearly demonstrates that most, if not all, such metastases are symptomatic and their clinical implications should not be overlooked. Notably, these metastases can be easily and safely resected using radioguided surgery.

Do primary neuroendocrine tumors and metastasis have the same characteristics?

BACKGROUND: Only one tumor site is usually biopsied to determine the histologic features of that patient's entire tumor burden. We hypothesized that there are significant histologic and functional differences in primary neuroendocrine tumors (NETS) and their nodal or organ metastases. We also hypothesized that limited tumor sampling could lead to erroneous assumptions about the tumor's histologic characteristics and clinical behavior. MATERIALS AND METHODS: Thirteen patients with metastatic well differentiated midgut NETS underwent simultaneous removal of their primary tumor, nodal metastasis, and organ metastasis. Each tumor site was stained quantitatively for Ki-67, chromogranin A (CGA), synaptophysin, CD31, and Factor VIII. Samples were also evaluated with in vitro tumor angiogenesis and drug chemoresistance assays. RESULTS: Ki-67 staining was nearly identical at all sites tested. Quantitative stains for CGA, synaptophysin, cluster of differentiation 31 (CD31), and Factor VIII varied considerably among the patient's three tissue site samples. Only 6% of the tissue samples tested against a battery of chemotherapeutic agents exhibited susceptibility to a single drug at all three tumor sites. In contrast, several antiangiogenic agents exhibited uniform effectiveness across all three tissue sites in multiple patients. CONCLUSIONS: Sampling only one NET tumor site may lead to erroneous assumptions about the tumor's histologic features and functional behavior. Evaluation of primary tumors and their nodal and organ metastasis may be necessary to optimize clinical decision making.