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Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)-positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18 F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18 F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated protein 1 and tankyrase 1 were upregulated, while beta-catenin, axin2, monocarboxylate transporter 8, and Frizzled 8 were downregulated. A positive relationship was found between 18 F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of 18 F-DOPA uptake correlating with LAT1 overexpression. We also demonstrated miR-375 overexpression and downregulated (Wnt) signaling and identified the Hippo pathway as a new potentially oncogenic feature of Pheo.

Objective: Laparoscopic adrenalectomy (LA) has become the gold standard technique for almost all the adrenal masses, but several Authors still debate about LA in pheochromocytoma., Background: The purpose of this study was to compare feasibility and safety of LA for pheo and analyze the results relative to LA for incidentaloma, Conn's disease and Cushing's disease., Methods: Between January 1994 and March 2006, 167 LAs were carried out in 160 consecutive patients at our Department and 46 of them were affected by pheo, 60 by Conn's disease, 34 by adrenal incidentaloma and 20 by Cushing's disease. The following parameters were statistically analysed: Side and size of lesion, conversion to open adrenalectomy (OA), operating time, length of hospital stay, intraoperative blood pressure variations, blood loss, blood transfusion, need for postoperative analgesia, resumption of oral nutrition and postoperative complications., Results: Successful LA was performed in 159 out of 167 cases (95.2%). Significant statistical advantages were observed for pheo, even if its average size was larger (p > 0.001), in terms of average operating time (p < 0.001), average length of hospital stay (p < 0.001), average intraoperative blood loss (p > 0.001), postoperative analgesia (p < 0.001), oral nutrition (p < 0.001). LA for patients with Cushing's disease (average length of hospital stay and intraoperative blood loss, p < 0.023 and p > 0.002 respectively) and with adrenal incidentaloma (intraoperative blood loss p < 0.009) seems to be a more challenging procedure., Conclusion: The evaluation of this relatively large monoinstitutional experience suggests that LA could be considered the most suitable method for removing pheochromocytoma. This tumour tends to be larger than most functional cortical adenomas, nevertheless it allows even a significant reduction in operating time with a faster recovery.

Background: Laparoscopic adrenalectomy has become the gold standard for removing adrenal masses, but several authors still debate the role of laparoscopic adrenalectomy in pheochromocytoma. The purpose of this study was to evaluate the short- and long-term outcomes of laparoscopic versus open adrenalectomy for pheochromocytomas and to compare the feasibility and safety of laparoscopic adrenalectomy for neoplasms that are smaller than 6 cm versus those that are larger than 6 cm., Methods: From January 1990 to December 2005, the same team in our department carried out 221 adrenalectomies in 211 patients. A total of 64 of these patients underwent 71 adrenalectomies for pheochromocytoma, 24 patients (37%) had open adrenalectomy, and 40 patients (63%) had laparoscopic adrenalectomy. Sex, age, side and size of lesion, operating time, duration of hospital stay, need for intensive care, intraoperative blood pressure variations, blood loss, postoperative analgesia, return to oral nutrition, and complications were compared among groups., Results: An advantage of laparoscopic adrenalectomy over open adrenalectomy was observed in mean operating time, hospital stay, need for intensive care, intraoperative hypertension, intraoperative blood loss, postoperative analgesia, and return to oral nutrition (P 6 cm) in laparoscopic adrenalectomy showed that none of the variables differed significantly, except for intraoperative blood loss, which was greater for the larger neoplasms (P = .007)., Conclusions: Laparoscopic adrenalectomy, when performed by experienced laparoscopic surgeons, is preferable to open adrenalectomy for the majority of pheochromocytomas, and as long as there is no evidence of invasion of surrounding structures, tumor size does not appear to have a profound effect on surgical outcome.

Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2+43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.

Adrenal surgery has been radically changed by laparoscopy and it is reasonable to wonder whether the increase in the number of adrenalectomies is entirely justified. There is still debate on the transperitoneal versus the retroperitoneal approach, the advantages and drawbacks of which are discussed here. Between 1983 and 2007, we performed 279 adrenalectomies in 264 consecutive patients, divided into two groups: before and after the advent of laparoscopic adrenalectomy (LA). We analyzed the factors that increased the number of adrenalectomies in recent years. The LAs were further divided into three consecutive periods and the morbidity and conversion rates, and mean operating times were compared. More procedures were performed after the advent of LA, i.e., 55 (19.7%) beforehand versus 224 (80.3%) afterwards, irrespective of the type of disease, for instance: incidentaloma, 17.6% versus 82.4% ( p < 0.0001); pheochromocytoma, 20.7% versus 79.3% ( p < 0.0001); Conn’s disease, 19.8% versus 80.2% ( p < 0.0001); Cushing’s disease, 17.2% versus 82.8% ( p < 0.0001); cortical carcinoma, 30% versus 70% ( p < 0.001). Analyzing the three LA periods, operating times were the only statistically significant variable ( p < 0.0001). The progressive increase in the number of adrenalectomies performed is due more to a better understanding of adrenal disease than to the availability of minimally invasive techniques. The choice of a laparoscopic approach (trans- or retroperitoneal) should depend on the surgeon’s experience. [ABSTRACT FROM AUTHOR]