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.

Tracking of blood pressure and its impact on graft function in pediatric renal transplant patients.

We studied tracking of BP and its impact on GFR in 44 PRTP followed for 56 months. Three months PT 77% had elevated SBP percentile. First year SBP and DBP correlated positively with final values (p < 0.0001, 0.0002, respectively). Pretransplant and three month PT SBP correlated positively (p = 0.02). At one yr, SBP and DBP were inversely associated with GFR (p = 0.002, p < 0.0001, respectively). SBP and BMI were positively associated at all time points. DBP was significantly higher in deceased recipients throughout the study period. Final DBP was higher (p = 0.03) and GFR lower (p = 0.04) in African-American patients. Patients with end-stage renal disease caused by glomerular disease had higher SBP (p = 0.03) and DBP (p = 0.04) than those with congenital malformations. GFR at one-yr PT (p = 0.02) and end of study (p = 0.003) was significantly lower in patients with high BP. Moreover, patients who maintained a normal systolic BP throughout the study had a significantly higher final GFR than those who were hypertensive at both time points [84 (normal BP throughout) vs. 52 mL/min/1.73 m(2) (high BP throughout), p = 0.02]. We conclude that PT hypertension is common in PRTP and predicts lower GFR.

Surgical treatment of advanced-stage carcinoid tumors: lessons learned.

OBJECTIVE: To evaluate clinical outcomes in a large group of advanced-stage carcinoid patients (stage IV) following multimodal surgical therapy. SUMMARY BACKGROUND DATA: Patients with advanced-stage carcinoid have traditionally experienced poor 5-year survival (18%-30%). Few recent series have evaluated a large number of patients treated with aggressive surgical rescue therapy. METHODS: This single-center retrospective review analyzes the records of 82 consecutive carcinoid patients treated by the same 2 surgeons, from August 1998 through August 2004 with a 3- to 72-month follow-up. RESULTS: Surprisingly, one third of 26 (32%) patients were found to have intestinal obstructions; 10 being moribund at presentation. Mesenteric encasement with intestinal ischemia was successfully relieved in 10 of 12 cases. Five of eighty-two "terminal" patients were rendered free of macroscopic disease. Karnofsky performance scores improved from 65 to 85 (P < 0.0001). Two- and four-year survival for patients with no or unilateral liver metastases (n = 23) was 89%, while 2- and 4-year survival for patients with bilateral liver disease (n = 59) was 68% and 52% (P = 0.072), respectively. CONCLUSION: We think that all patients with advanced-stage carcinoid should be evaluated for possible multimodal surgical therapy. Primary tumors should be resected, even in the presence of distant metastases to prevent future intestinal obstruction. The "wait and see" method of management of this slow-growing cancer no longer has merit. We offer an algorithm for the surgical evaluation and management of these patients.

Chronic rejection: the next major challenge for pancreas transplant recipients.

OBJECTIVE: With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. METHODS: We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. RESULTS: A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P=0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P<0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P=0.002), cytomegalovirus infection posttransplant (RR=2.41, P=0.001), a retransplant (versus primary transplant) (RR=2.27, P=0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P=0.04). CONCLUSIONS: As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.

Long-term (20-37 years) follow-up of living kidney donors.

Numerous studies with <20 years of follow-up have shown no significant long-term consequences of living kidney donation. However, hypertension and proteinuria have both been described; it is unknown whether either complication presages future kidney dysfunction. Between June 1, 1963, and December 31, 1979, we did 773 living donor kidney transplants for 715 recipients. We attempted to contact all donors to determine long-term outcome regarding their remaining kidney. We obtained information on 464 (60%) of the donors. Of these, 84 had died and 380 were alive; of the 380, 256 returned a questionnaire and 125 sent in current laboratory results and/or records of a recent history and physical examination. Of the 84 donors who had died, three were known to have had kidney failure. Of the 380 still alive, three had abnormal kidney function and two had undergone transplantation. The remaining donors had normal kidney function. The rate of proteinuria and hypertension was similar to the age-matched general population. We conclude that most kidney donors have normal renal function 20-37 years post donation. However, some do develop renal dysfunction; some, renal failure. Our data underscore the need to develop prospective trials for long-term follow-up of kidney donors.