Long-term follow-up for pilonidal sinus surgery: A review of literature with metanalysis.

BACKGROUND: Sacrococcygeal pilonidal sinus disease (PSD) is a common chronic inflammation of the natal cleft and presents as an abscess or a chronically discharging, painful sinus tract. The management of chronic PSD is variable, contentious, and problematic. Although many surgical procedures have been tried, the best surgical method remains controversial. The aim of this systematic review with meta-analysis of literature is to provide surgeons an objective instrument of decision through an analysis of recurrence rate of various surgical techniques in a long-term follow-up. METHODS: Systematic literature searches were performed to identify all available studies. According to the pre-specified protocol, all studies reporting a surgical approach to PSD with a minimum follow-up of 5 years were included. RESULTS: Fifteen studies were included in the analysis. The number of patients varied from 50 to 1165 with a mean follow-up from 58.36 to 240 months. The overall incidence of recurrence was of 0.138; the resulting incidence of open healing, midline closure and out-midline closure were of 17.9%, 16.8% and 10% respectively. CONCLUSIONS: Interestingly, our data reveal a rate of relapsing disease higher than the one defined in previous studies both for the overall PSD and for each surgical procedure. A long-term follow-up of at least 5 years, should be considered the gold standard in pilonidal sinus surgery benchmarking. From our results, we can state that open healing and midline closure should not be considered effective for their high frequency of relapse disease and midline primary closure should be preferred.

A technical modification of video-assisted ablation for recurrent pilonidal sinus.

AIM: The study evaluated, in a proof of concept, the usefulness of a prosthesis (plug) in addition to video assisted ablation of pilonidal sinus (VAAPS) for treatment of recurrent pilonidal sinus. METHOD: This is a case series of recurrent complex pilonidal sinus treated by VAAPS plus plug positioning. RESULTS: Four patients were analysed. All were successfully treated by this new approach. No difficulties in inserting the plug were identified. Complete healing was achieved in all cases. No infection or recurrence was reported during a limited follow-up. CONCLUSION: This new technique allows a minimally invasive scarless approach to recurrent pilonidal sinus.

An early onset of acute renal failure in a young woman with obesity and infertility who underwent gastric balloon positioning. A case report.

INTRODUCTION: Although intragastric balloons have been in use for several years to achieve weight reduction in obese patients, acute renal failure after gastric balloon positioning is reported in few studies CASE REPORT: A 32-year-old white infertile woman undergone Bioenterics Intragastric Balloon (BIB) positioning in an attempt to weight loss and improve her fertility status. After only six days of persisting vomiting acute renal failure was found. A complete recovery of renal function was obtained after 14 days. CONCLUSION: Acute renal failure was due to persistent vomiting leading to dehydration. Physicians involved in BIB patients management must consider the possibility of major complications in all hyperemetic subjects. BIB removal, with a concomitant intravenous fluid replacement and minerals or vitamins supplementation has to be taken into account as an emergency procedure.

Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases.

INTRODUCTION: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. AIM: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. PATIENTS AND METHODS: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. RESULTS: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. CONCLUSIONS: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

The role of drainage after excision and primary closure of pilonidal sinus: a meta-analysis.

We carried out a systematic review of the literature to identify the association between the use of drain and the incidence of infections and recurrences after surgery. MEDLINE, SCOPUS and ISI databases were searched up to September 2012. The two outcomes of this meta-analysis were wound infection and recurrence. Postoperative wound infection occurred in 50 of the 604 (8.28 %) patients who underwent drainage and in 68 of the 598 (11.4 %) patients who did not, with a resulting odds ratio (OR) of 0.71 (95 % CI: 0.48-1.03). Recurrence of pilonidal sinus occurred in 41 of the 604 (6.79 %) patients who underwent drainage and in 50 of the 598 (8.36 %) patients who did not, with a resulting OR of 0.80 (95 % CI: 0.52-1.23). The results suggest that, despite a trend toward a reduction in infectious complications and recurrence, drainage was not associated with a better outcome. However, because of the present literature's limitations, further studies are needed to address this issue.

Outpatient surgical procedures: which is the ideal teaching procedure for a resident surgeon?

AIM: The aim of our study is to evaluate which surgical procedures can be considered the ideal teaching procedure for a resident surgeon. MATERIALS AND METHODS: This is a retrospective study. A chart review was performed on all patients who underwent inguinal hernia repair, saphenectomy, excision of pilonidal sinus and hemorrhoidectomy at our institution, between September 2000 and July 2011, and have at least 1 year of follow-up. We evaluated operative time and complications comparing the results obtained by resident or attending surgeon. RESULTS: We obtained a higher operative time among the procedures performed by resident surgeons for all evaluated interventions. Whereas the occurrence of complications after hernia repair and excision and primary closure of pilonidal sinus were similar in case and control subjects (p = 0,1 and p = 0,1), the occurrence of complications after hemorrhoidectomy and saphenectomy was significantly higher in the case group (p = 0,08 and p = 0,1). CONCLUSION: Hernia repair and excision and primary closure of pilonidal sinus have to be considered the ideal teaching procedure in a residency program, giving to the young surgeon the opportunity of reach several skills that he needs to master most difficult surgical procedures. Saphenectomy and hemorrhoidectomy should be considered safe only if performed by a senior resident surgeon.

Safety and efficacy of saphenectomy in elderly patients.

AIM: The aim of this study is to evaluate safety and efficacy of saphenactomy in elderly patients. PATIENTS AND METHODS: A total of 358 patients with varicose veins of the lower limbs treated between January 2001 and December 2011. 213 of these were patients under 65 years old and 145 patients were over this age. We have evaluated short- and long-term complications to compare the results among young and elderly patients. RESULTS: Postoperative complications that occurred were: infection, haematoma, nerve injury (paresthesia and pain) and deep vein thrombosis. Although a trend towards better results was observed among the young patients, no significant differences were shown in our experience. CONCLUSION: Elective saphenectomy has a good outcome also in the elderly patients. The slightly higher rate of complications that occurred in older patients is not significant and does not support advising against the use of this surgical approach in the elderly. So in our opinion saphenectomy is quite safe and feasible also in patients over 65 years.

Clinical and prognostic implications of the genetic diagnosis of hereditary NET syndromes in asymptomatic patients.

Neuroendocrine tumors (NETs) can be sporadic or they can arise in complex hereditary syndromes. Patients with hereditary NETs can be identified before the development of tumors by performing genetic screenings. The aim of the study was to evaluate the clinical and prognostic impact of a preclinical genetic screening in subjects with hereditary NET syndromes. 46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs). The main outcome measures were severity of disease, prognosis, and survival. The rate of surgery for MEN1-, MEN2-, FPGL4-related tumors was 90% in group A and 35% in group B (p<0.01). Both symptoms related to tumors and symptoms related to therapies were significantly less frequent in group B than in group A (p<0.05). Tumor stage was locally advanced or metastatic in 50% of group A and in no one of group B (p<0.01). The mortality rate was 25% in group A and 0% in group B (p<0.05). An early genetic screening for hereditary NET syndromes results in an improvement in clinical presentation and morbidity. A potential impact of the genetic screening on the mortality rate of these subjects is suggested and needs to be investigated in further and more appropriate studies.

Screening of pancreaticoduodenal endocrine tumours in patients with MEN 1: multidetector-row computed tomography vs. endoscopic ultrasound.

PURPOSE: The authors compared multidetector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) in the identification of pancreaticoduodenal endocrine tumours (PETs) in patients with multiple endocrine neoplasia type 1 (MEN 1). MATERIALS AND METHODS: Fourteen consecutive patients (eight men and six women, aged 26-54 years) with MEN 1 underwent MDCT performed with a 4- (n=5) or 64- (n=9) detector-row system and EUS done with a radial transducer (7.5-20 MHz) within 7-28 days of each other. Prior to MDCT examination, patients were given 750 cc of water and asked to lie down in the right lateral decubitus for 15 min. Multiphase MDCT images were acquired both before and after the injection of nonionic iodinated contrast material (2 cc/kg) at an injection rate of 4 ml/s, with technical parameters and scan delay varying in relation to the system used. Images were all reconstructed at 3-mm intervals for the three phases (arterial, pancreatic and portal) and evaluated on a dedicated workstation. RESULTS: MDCT detected a total of 25 PETs (3-18 mm) in nine patients. Of these lesions, nine were situated within the duodenal wall and 16 in either the pancreatic head (n=3), body (n=7), or tail (n=6). Three additional lesions were detected retrospectively after EUS imaging. Most (18/22, 81%) were hypervascular nodules, and four appeared as either hypoattenuating or cystic lesions. EUS detected a total of 32 PETs (2-18 mm) in 11 patients. Most lesions (29/32, 90%) appeared hypoechoic and were situated in the duodenal wall (n=15) or in either the pancreatic head (n=10), body (n=6) or tail (n=1). CONCLUSIONS: Our preliminary data indicate that MDCT is complementary to EUS in the identification of PETs in MEN-1 patients.

Recurrent varicose veins of the lower limbs after surgery. Role of surgical technique (stripping vs. CHIVA) and surgeon's experience.

BACKGROUND: Surgical treatment of varicose veins of the lower limbs resolves symptoms and improves quality of life. However, the high recurrence (20-80%) is a costly and complex issue. PATIENTS AND METHODS: This is a retrospective review of 1489 patients with varicose vein of the lower limbs seen at our hospital between January 1980 and December 2005. The aim is to evaluate the effect of surgical technique (stripping vs. CHIVA) and surgeon's experience in reducing recurrences. RESULTS: With experienced surgeons, CHIVA appears to be more effective than stripping in reducing the recurrence rate (p <0.05). However, when performed by an inexperienced surgeon the results are far worse than those achieved with stripping. CONCLUSION: There was a clear reduction in recurrences at 5-10 years with CHIVA than with conventional stripping. However, if performed incorrectly, results are far worse with CHIVA. In fact, good results are far more difficult to achieve with CHIVA than with stripping, which is repeatable and easy to perform.

Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels.

BACKGROUND AND OBJECTIVES: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. PATIENTS AND METHODS: Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. RESULTS: A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0.002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. CONCLUSIONS: A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.

[Hernia repair and local anesthesia. Results of a controlled randomized clinical trial]. / Ernioplastica inguinale e anestesia locale. Risultati di uno studio randomizzato e controllato.

In the past, general and spinal anesthesia were used for hernia surgery, but nowadays local anesthesia has become the method of choice for hernia repair, especially in outpatient patients. The one-day surgery is sufficient in the management of this pathology. The advantages of local anesthesia are simplicity, safety, extended postoperative analgesia, early mobilization, lack post-anesthesia effects, and low costs. From January 2004 to December 2008 we observed 297 male patients with inguinal hernia. These patients were divided, with rigorous chronological order of hospital admission, in two study groups, different for anesthetic techniques used. Our controlled randomized clinical trial examines the effectiveness of local anesthesia to reduce the time of hospitalization, without alteration of results, and particularly the degree of satisfaction of patients surgical treated for inguinal hernia.

Intracorporeal versus extracorporeal anastomosis after laparoscopic gastrectomy for gastric cancer. A systematic review with meta-analysis.

AIM: To perform a systematic review and meta-analyses of studies comparing the totally laparoscopic procedures with intracorporeal anastomosis (IA) to laparoscopic-assisted surgery with extracorporeal anastomosis (EA) in gastric resections. METHODS: We performed a systematic search in the electronic databases. Outcomes analysed were: intraoperative (operative time and intraoperative blood loss), oncologic (harvested nodes, distance of the tumour from proximal and distal margin), postoperative complications (gastric stasis, intraluminal and extraluminal bleeding, leakage and wound infection) recovery (time to first flatus, time to first oral intake and hospital stay). We performed meta-regression analyses after implementing a regression model with the analysed outcomes as dependent variables (y) and the demographic and pathologic covariates as independent variables (x). RESULTS: A total of 26 studies (20 on distal gastrectomy and 6 on total gastrectomy) were included in the final analysis. Regarding distal gastrectomy, there was no statistical difference between the two groups in the above-mentioned outcomes, except for intraoperative blood loss (less in IA group, P=0.003), number of harvested nodes (better in the IA group, P=0.022) and length of hospital stay (shorter in the IA group, P=0.037). Regarding total gastrectomy, there was no statistical difference for all outcomes, except for the distal margin (further in the EA group, P=0.040). Meta-regression analysis showed that a lot of variables influenced results in distal gastric resections, but not in total gastric resections. CONCLUSION: We can state laparoscopic gastric resections with IA are safe and feasible when performed by expert surgeons. However, new well-designed studies comparing the two techniques are needed to confirm the benefits of laparoscopic IA.

Comparison between LigaSure™ and Harmonic® in Laparoscopic Sleeve Gastrectomy: A Single-Center Experience on 422 Patients.

Background: New laparoscopic devices, such as electrothermal bipolar-activated devices (LigaSure™ (LS)) or ultrasonic systems (Harmonic® scalpel (HS)), have been applied recently to bariatric surgery allowing to reduce blood loss and surgical risks. The aim of this study was to retrospectively compare intraoperative performance of HS and LS, postoperative results, and clinical outcomes in a large cohort of patients undergoing LSG. Methods: Data from 422 morbidly obese patients undergoing LSG in our Bariatric Unit at the Advanced Biomedical Sciences Department of the "Federico II" University of Naples (Italy) between January 2009 and December 2017 were retrospectively analyzed. Subjects were divided into two groups (HS and LS), and operative time, intraoperative complications, and postoperative (within 30 days from surgery) complications were compared. Bleeding from the omentum or from the staple line, use of hemostatic clips, and absorbable hemostat were recorded as intraoperative complications; hemorrhages, abscess formation, gastric leaks, fever, and mortality were considered as postoperative complications. Results: Statistical analysis showed no difference in terms of baseline demographics between the two cohorts. Operative time (48 ± 9 vs 49 ± 6 min, p=0.646) and the rates of intraoperative and postoperative complications did not significantly differ between groups. Conclusion: Harmonic® and LigaSure™ are both useful tools in bariatric surgery, and these two advanced power devices are user-friendly and can facilitate surgeon work; from this point of view, the choice of the energy device should be based on the preference of the surgeon and on the hospital costs policy and availability.

Diagnostic and prognostic implications of the World Health Organization classification of neuroendocrine tumors.

BACKGROUND: Neuroendocrine differentiation of tumors is often difficult to establish. In the same manner, the evaluation of the prognostic role of neuroendocrine differentiation may constitute a relevant clinical problem. Although different classifications are used for neuroendocrine tumors (NET) of different origin, the last World Health Organization (WHO) classification of NET, originally proposed for gastroenteropancreatic tumors, has proved to be a practical tool to allow pathologists to uniform the diagnoses and re-classify these tumors into 3 main categories. AIM: The present study was carried out in order to evaluate diagnostic and prognostic implications of NET reclassification according to the last WHO classification of NET. MATERIALS AND METHODS: Thirty-one tumors with an initial diagnosis referable to a NET achieved before 1999 were independently evaluated by 3 pathologists on the basis of the 2000 WHO classification of NET. Immunohistochemistry for panneuroendocrine markers and Ki-67 was also performed in all cases. RESULTS: Twelve, 14, and 4 tumors were respectively reclassified as well-differentiated NET, well-differentiated neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma; 1 tumor was reclassified as mixed endocrine-exocrine tumor. Two or more neuroendocrine markers were expressed in all NET regardless of histotype, differentiation degree, and site of primary tumor. After revision, 10 of the 31 tumors under study (32%) changed histo-prognostic category when compared to the initial diagnosis. Ki-67 score was the best predictor of survival at the multivariate analysis. CONCLUSION: The WHO classification is suitable to accurately reclassify tumors with an initial diagnosis referable to a NET and to separate these tumors in 3 well-distinct histo-prognostic categories with relevant clinical implications. Ki-67 score seems to be a better predictor of survival than the degree of differentiation.

The biological characterization of neuroendocrine tumors: the role of neuroendocrine markers.

Neuroendocrine tumors (NET) may originate in different organs, from cells embryologically different but expressing common phenotypic characteristics, such as: the immuno-reactivity for markers of neuroendocrine differentiation (defined as "pan-neuroendocrine"), the capacity to secrete specific or aspecific peptide and hormones and the expression of some receptors, that are at the basis of the current diagnostic and therapeutical approach, peculiar to these tumors. NET have been conventionally distinguished in functioning, when associated with a recognized clinical endocrine syndrome, and non-functioning. However, this terminology may be misleading, since the great majority of NET may secrete neuroendocrine peptides, which can be employed as clinical markers for both diagnosis and follow-up. On the other hand, tissue immuno-reactivity for specific hormones does not always reflect secretory activity of the tumor cells. Finally, receptors and genetic markers are acquiring a relevant role in the characterization of NET, both improving knowledge of biology and physiopathology of NET, as well as in developing specific strategies to establish an early diagnosis and targeted therapies, to adopt prophylactic strategies in familial forms, and to identify more efficacious targets for therapy in the future.

Case report of a conservative management of cervical esophageal perforation with acrylic glue injection.

BACKGROUND: perforation of the upper aerodigestive tract is a potentially life-threatening condition. The appropriate treatment of cervical esophageal perforation is still controversial. CASE PRESENTATION: we report a case of cervical esophageal perforation that was effectively treated by a conservative management with acrylic glue injection. DISCUSSION: the management of cervical esophageal perforations has been controversial and little studied. Various treatment options, including surgical and nonsurgical management have been advocated, and no gold standard surgical treatment has yet been established. Some authors have recommended immediate surgical intervention, especially in penetrating trauma, conversely, several studies support conservative management. CONCLUSIONS: we consider that the application of acrylic glue can be considered a promising, minimally invasive therapeutic option in the management of cervical esophageal perforation. However, the sufficient accumulation of similarly treated cases is necessary in order to confirm the efficacy and safety of this treatment modality.

Case report of an uncommon case of drain-site hernia after colorectal surgery.

BACKGROUND: trocar site herniation is a rare but potentially serious complication of laparoscopic surgery. Data about drain site hernia after laparoscopic surgery is scarce and anecdotal. CASE PRESENTATION: we report an uncommon case of drain site hernia in a man undergone laparoscopic left colectomy for a colonic adenocarcinoma who developed small bowel herniation in a 10 mm port site, in which a 24 FR drain was inserted leaving a real free space of 2 mm. DISCUSSION: laparoscopic approach has gained widespread acceptance in each surgical fields because of the perceived better postoperative outcomes in terms of less pain, faster recovery, and lower risk of incisional hernia. However, the risk of trocar site hernia has been known since 1967. Different risk factors for the development of trocar site hernia are described in literature: the trocar diameter and design, preexisting fascial defects, enlargement of a port site to remove a specimen, high blood glucose levels, obesity, increase intra-abdominal pressure as in chronic obstructive airway disease or extensive manipulation of the trocar during surgical intervention, which may enlarge the trocar site and thus induce small bowel herniation. However, the most important recognized risk factor for trocar site hernia is the size of the trocar. CONCLUSIONS: waiting for further studies, the lesson to be learnt from this case report is that, even if the free space after drain positioning is minimal, drain should not be positioned through the 10 mm trocar to allow the closure of fascial defect in order to avoid any herniation.

Safety and efficacy of laparoscopic wedge gastrectomy for large gastrointestinal stromal tumors.

BACKGROUND: Although the feasibility of minimally invasive resection of small gastric GISTs is well established, less is known about safety and efficacy of laparoscopic surgery for large tumors. METHODS: A retrospective analysis was performed, using a prospectively maintained comprehensive database. Patients were divided into two groups according to tumor size: Case group with tumors > 5 cm and control group with tumors <5 cm. Hospital charts were reviewed, and various outcome measures recorded, including operative time, estimated operative blood loss, post-operative leak, stasis, infection and recurrence. RESULTS: No tumors were ruptured during surgical manipulation and no major morbidity or mortality occurred in either group. Operative time (75,8 ± 33,1 min in large cases vs 75,8 ± 33,1 min in small cases) was similar in both groups (p = 0,61). The incidence of post-operative complications did not differ between the two groups. In details there were 21 out of 25 (84%) uncomplicated cases among small GISTs versus 17 out of 24 (70,8%) uncomplicated cases among large GISTs (p = 0,32). CONCLUSION: This matched-pair case control study demonstrates that laparoscopic wedge resection for large gastric GISTs is safe and effective, as demonstrated for small tumors.

Endocrine dysfunction in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is a genetic disorder caused by lysosomal alpha-galactosidase-A deficiency and is characterized by the systemic accumulation of globotriaosylceramide. All endocrine glands are susceptible to globotriaosylceramide accumulation because of their high vascularization and low cellular proliferation rate. Nevertheless, this endocrine system has never been investigated in detail. OBJECTIVE: We aimed to investigate the function and morphology of the endocrine glands in FD. PATIENTS: The thyroid, gonadal, adrenal, and GH/IGF-I axes were evaluated in 18 FD patients (nine females and nine males, aged 21-64 yr) and 18 sex- and age-matched healthy subjects. STUDY DESIGN: We conducted an observational, analytical, open, prospective study. INTERVENTIONS: Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase-A (agalsidase beta) at a dose of 1 mg/kg body weight every 2 wk. RESULTS: FD patients had higher baseline TSH levels than controls (P < 0.01). Three subjects were diagnosed with an early stage of subclinical primary hypothyroidism associated with negative antithyroid antibodies. A history of menses abnormalities, miscarriage, or assisted delivery was found in 89% of FD women. Asthenozoospermia, oligozoospermia, or both were found in all FD men through seminal fluid analysis. FD patients had significantly higher circulating ACTH and lower cortisol levels than controls (P < 0.05). In patients under ERT, a suboptimal cortisol response to the 250-microg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P < 0.05). CONCLUSION: A variety of latent endocrine dysfunctions, including life-threatening conditions, occur in patients with FD. Endocrine dysfunctions are also present in patients already receiving ERT and are in part related to their persistent poor quality of life. An endocrine work-up should be recommended in all FD patients. Adequate monitoring and hormonal therapy, when required, have to be performed in cases of subclinical endocrine dysfunction to avoid life-threatening events.