Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men.

PURPOSE: In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery. METHODS: Hypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies. RESULTS: In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones. CONCLUSIONS: The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.

Cell proliferation, cell death, E-cadherin, metalloproteinase expression and angiogenesis in gastric cancer precursors and early cancer of the intestinal type.

The aim of this study was to analyse the morphological, kinetic and molecular characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in comparison with intestinal metaplasia type III (IM III) and normal mucosa (NM) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGC, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic index (AI) were assessed. The E-cadherin expression (E-Cad), matrix-metalloproteinase activity (MMP2), and the number of microvessels (NV) were also evaluated. Among the categories, MI increases from NM to IM III and LGD, and from LGD to HGD and EGC, while AI continues to increase also from HGD to EGC. E-cad decreases from NM to EGC, although not significantly from LGD to HGD; MMP2 is significantly more expressed only in EGC. Three groups are obtained by means of cluster analysis. The first group includes all the NMs and IM IIIs, all except 1 LGD, about half of HGDs, and 1 EGC. E-Cad is highly expressed, MMP2 and angiogenesis are low, the proliferative activity is low and mitoses are partly balanced by apoptoses. The second group includes some EGCs and HGDs and is characterised by a very high proliferative activity and cell death; there is an initial loss of cell adhesion, an increase of MMP2 and NV. The third group includes the majority of EGCs, but also 1 HGD: it has intermediate MI and AI, the lowest expression of E-Cad, the highest expression of MMP2 and the most numerous microvessels. These results underscore the necessity of evaluating each case individually within the same singular category of Correa's sequence. The use of kinetic and molecular parameters in addition to the morphological analysis may give important information on the behaviour of the various lesions.

Cell kinetic patterns in early gastric cancer.

Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same parameters discriminate among intestinal type tumors, when separately considered from diffuse ones. No correlation is noted of these 2 groups with transforming growth factor-alpha, epidermal growth factor receptor and p53 expression, gross type, entity of neoangiogenesis, and submucosal invasion.

Simultaneous total aortic replacement from valve to bifurcation: experience with 21 cases.

From June 1985 to December 1991, 21 patients (12 men and 9 women; mean age, 60 years) underwent total simultaneous aortic replacement that extended from the valve to the bifurcation. The causes of the diseased aorta were: medial degeneration with total aortic dilatation or multiple aneurysms (n = 7) and either acute (n = 4) or chronic (n = 10) dissection. Clinical evaluation and investigation in all patients consisted of computed tomography and magnetic resonance imaging as well as angiography. Only patients with combined thoracic and abdominal emergencies were selected, and these comprised worsening of cardiac conditions resulting from aortic regurgitation, and rapid dilatation of the ascending aorta and arch with impending rupture in conjunction with ischemia of the abdominal viscera, kidney, or either leg. The surgical technique consisted of inducing deep hypothermia by means of femoral vein-femoral artery cardiopulmonary bypass. During the cooling time, the aortic root was replaced under cardioplegia. Once lowering of the body temperature attained electroencephalographic silence, circulation was stopped and the aorta was replaced from the arch to the bifurcation. Circulation and rewarming were resumed only after the operation was completed. In our most recent patient, the operating time was reduced by opening the thoracic and the abdominal incisions during cooling; the cardioplegic solution as not injected but, instead, the myocardium was cooled down along with the whole body. In these patients, the hypothermy at electroencephalographic silence ranged from 14 degrees to 19 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Excision of the aortic wall in the surgical treatment of acute type-A aortic dissection.

Between March 1986 and September 1988, 38 patients underwent extended aortic resection (aortic valve, ascending aorta, and arch) for acute type-A aortic dissection with aortic valve insufficiency; deep hypothermia and circulatory arrest were used. All patients were operated on within 17 hours of the onset of symptoms. In the first 24 patients, operation was performed by the "inclusion technique." In the last 14 patients, the "excision technique" was used: the ascending aorta and arch was excised, and the aorta was transected at the beginning of the descending thoracic tract. Excision and transection were considered essential to prevent back flow from the false lumen, which is the main source of bleeding, and to allow all anastomoses to be constructed beyond the limits of dissection. The only anastomosis to the dissected aorta was at the distal end of the graft. One of the 14 patients died (7.1%). One patient was reopened for bleeding: blood was issuing from the attachment of the carotid trunks, and the defect was repaired by interposing a bifurcated Dacron graft between the arch graft and the carotid arteries. Extended aortic excision meets the principle of either eliminating as far as possible the diseased aorta or controlling intraoperative and postoperative bleeding. An operation of great magnitude can be considered a life-saving procedure when compared with the high risk of acute type-A aortic dissection.

Extended and total aortic resection in the surgical treatment of acute type A aortic dissection: experience with 54 patients.

Fifty-four patients with acute type A aortic dissection were surgically treated with extended aortic resection. The age of the patients ranged from 22 to 75 years, and all of them were in very critical condition. In 50 patients, the resection extended from the aortic valve (included in 33) to the beginning of the descending thoracic aorta and in 4, from the valve (included in 3) to the aortic bifurcation. Deep hypothermia and circulatory arrest were employed during the aortic arch resection; inclusion of the graft at the end of procedure was done in 44 patients; in the others, the diseased aortic wall was excised. Early mortality was 20 +/- 6% (11/54). Nine deaths were due to persistence of the distal dissection. Acute type A aortic dissection with aortic valve insufficiency should be treated as an emergency with extended aortic resection. As far as control of bleeding and closure of distal dissection are concerned, the best results have been achieved when the diseased aortic wall has been completely excised.

Kinetic patterns in advanced gastric cancer as related to histotype and tumor extension.

Kinetic patterns of advanced gastric cancers were analyzed for comparison between intestinal- and diffuse-types by using the mean values of mitotic index (MI), apoptotic index (AI), the sum of the two [i.e., the turnover index (TI)] and growth index (GI), and the values of the same parameters in the three layers (upper, intermediate, lower) in which cancers were subdivided from surface to depth. Site and extent of tumors, lymph node invasion, and p53 and PCNA expression were not different between the two histotypes; tumor cell dissociation (TCD) was higher in diffuse-type cancers. Mean MI, AI, TI, and GI were not different between the two histotypes, while MI, AI, TI, and GI were higher in the upper layer of intestinal-type cancers than in that of diffuse-type. MI and GI decreased while AI increased from upper to deeper layers in intestinal-type tumors; MI, AI, and TI increase from upper to lower layers in diffuse-type tumors. In intestinal-type cancers, but not in diffuse cases, TI and GI were higher in the T2 group than in T3. This different behavior between the two histotypes is discussed.

The influence of new technologies on laparoscopic adrenalectomy: our personal experience with 91 patients.

BACKGROUND: Laparoscopic adrenalectomy has proved to be the technique of choice for managing benign pathologies of the adrenals and isolated adrenal metastases, especially those arising from lung tumor, but the procedure should not be performed for primitive adrenal carcinoma. The Authors wanted to test the advantages of the Harmonic Scalpel in laparoscopic adrenalectomy. METHODS: From April 1995 to April 2001, the authors investigated their series of laparoscopic adrenalectomies performed at the Careggi General Hospital, Division of General and Vascular Surgery, Florence, Italy. This study enrolled 91 patients with various adrenal pathologies. The transperitoneal approach was used, with the patient in a lateral position, as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals by the use of new technological devices such as the Harmonic Scalpel. The operative time required by the surgical procedure was computed by dividing the study into three periods: 1995-1997, 1998-1999, 2000-2001. The first period was necessary to complete the learning curve. In the second period, a steady state in surgical time was reached. During the third period, the Harmonic Scalpel was introduced. The differences between the three periods were tested using a nonparametric analysis (Mann-Whitney U test or Kruskal-Wallis test) as appropriate. A two-tailed p value of 0.05 or less was considered statistically significant. The authors investigated the cost of the operation performed in each of the two groups using, respectively, the conventional laparoscopic device (1998-1999) and the Harmonic Scalpel (2000-2001). The following expenses were considered: Harmonic Scalpel impulse generator and disposable shears, operating room cost per hour, and endoclip applier. RESULTS: The 91 laparoscopic adrenalectomies were performed with these indications: 31 incidentalomas (26 adenomas and 5 cysts), 25 cases of Conn's disease, 18 cases of Cushing's disease, 9 pheochromocytomas, 2 myelolipomas, 5 metastases (from lung, kidney, and breast) and 1 primitive carcinoma diagnosed preoperatively. Considering the whole series (1995-2001), there was a significant trend of reduction in operative time (p = 0.0001). Moreover looking at the first period (1995-1997), in which the learning curve was completed, the mean surgical time was 148 min, as compared with 125 mm. For the second period (1998-1999) (p = 0.0002). This represents a significant reduction in operative time. The authors noted a further reduction in the operative time when surgery was performed with the Harmonic Scalpel (2000-2001) (92 min; p = 0.001). The reduction in operative time attributable to the Harmonic Scalpel was confirmed also by a multivariate analysis of covariance general linear models procedure (GLM), which accounts for several confounders: age, gender, site and size of tumors, and histology (p = 0.0001). The rate was 3.3% for morbidity, 1.1% for mortality, and 2.2% for conversion. There was no difference in complications between patients treated with conventional devices and those treated with the Harmonic Scalpel. CONCLUSIONS: The laparoscopic approach has proved to be an extremely reliable procedure for benign pathologies and isolated metastases. There may yet be doubts about its use for the treatment of adrenal carcinomas preoperatively diagnosed. When surgery is performed using Harmonic Scalpel, operative time is significantly reduced and surgery is easier and less expensive. Infact use of the Harmonic Scalpel allowed the cost per operation to be reduced $70. Moreover, if surgery is performed using the nondisposable clip applier, the expenses are reduced $105.

Villous adenoma of the bladder.

Villous adenomas of the bladder are rare tumors and up to now they have not been seen to undergo malignant transformation. We report a case of villous adenoma of the bladder with areas of adenocarcinoma in a 72-year-old man. We describe all the morphological, histochemical and immunohistochemical features characterizing this tumor. We recommend adequate pathological sampling and a thorough follow-up of patients with villous adenoma. The prognosis and the behaviour of these adenomatous papillary lesions, morphologically similar to colonic adenomas, in the bladder is unclear. We report a case with focal area of adenocarcinoma and review the literature.

Coronary reconnection in emergency "conduit operation" for acute type-a aortic dissection with aortic insufficiency: experience with 24 cases.

Twenty-four cases of acute type-A aortic dissection with aortic valvular insufficiency were treated in our institution by means of an emergency operation in which the aortic valve, ascending aorta, and aortic arch were resected and replaced with a valved conduit that had been lengthened with a tubular Dacron graft. The procedure included the use of deep hypothermia for cerebral protection, as well as extracorporeal circulation. Aortic resection was performed from the aortic valve to the origin of the descending thoracic aorta; the aortic graft was anastomosed proximally to the valve annulus and distally to the descending aorta. The carotid orifices were connected to the side of the graft in a single tissue button. The coronary arteries were then reconnected by means of double venous bypass grafts to the innominate artery, to allow for inclusion of the graft. Within 1 month after operation, four patients died of the consequences of dissection. Six months postoperatively, one patient succumbed to an infarction. Six months to 5 years after operation, the remaining 19 patients are still alive. On the basis of this experience, we believe that acute type-A aortic dissection with aortic valvular insufficiency should be treated during the first hours after the onset of symptoms. The above-described procedure proved effective in the control of bleeding, which is the major risk in emergency operations of this type.

[Extensive lymphadenectomy in the therapy of cancer of the left colon and rectum: an analysis of the anatomicopathological data]. / La linfectomia allargata nella terapia del cancro del colon sinistro e del retto: analisi dei dati anatomo-patologici.

In the last 12 years in our surgical service, radical resection was performed in 142 patients with cancer of left colon and in 145 patients with rectal cancer. Extended lymphadenectomy was always realized: preaortocaval lymphadenectomy in colonic cancer; preartocaval and pelvic lymphadenectomy in rectal cancer. The incidence of C stage was 40.14% in cancer of left colon and 40.68% in rectal cancer. Neoplastic diffusion in preaortocaval lymph nodes was only in a patient with colonic cancer, never in patients with rectal cancer. The incidence of neoplastic diffusion in pelvic nodes was 3.12% (0 in superior rectum; 6.25% in medium rectum; 2.4% in inferior rectum). In 1 of 90 patients with tumour of medium or inferior rectum, we relieved tumoural involvement of pelvic nodes without neoplastic diffusion in regional nodes. These anatomo-pathological data subline: a) the low incidence of neoplastic diffusion in preaortocaval nodes in cancer of left colon and rectum; b) the importance of pelvic lymphadenectomy in cancer of medium and inferior rectum.

[Laparoscopic approach to the "acute" and "chronic" bowel obstruction]. / Approccio laparoscopico alle occlusioni "acute" e "croniche" del piccolo intestino.

AIM OF THE STUDY: To retrospectively evaluate a series of patients with acute and chronic small bowel obstruction and discuss the indications of laparoscopic vs laparotomic approach and the outcome of both these techniques. PATIENTS AND METHOD: 85 patients with acute and chronic small bowel obstruction who underwent to either emergency or elective surgery since January 1999 up to October 2001 were enrolled. Subjects were divided into three groups: 39 treated with emergency laparotomy (group I), 13 with emergency laparoscopy (group II) and 33 with elective laparoscopy for chronic/subacute obstructions (group III). RESULTS: 1) the most frequent indication of the laparotomic approach was either multiple or major previous surgery as well as neoplastic diseases; 2) patients of the second group had frequently previous either minor or laparoscopic surgery; 3) the incidence of previous emergency surgery were maximum among the III group; 4) both post-operative ileus and mean hospital stay lasted less in the II than in the I group. The mean operative time and the morbidity was equal in the two groups; 5) we observed more intra-operative complications, a higher conversion rate and a longer both post-operative ileus and mean hospital stay in the II than in the III group. CONCLUSIONS: Our data support the role of laparoscopy in patients with chronic/subacute small bowel obstruction. Patients with acute obstruction may undergo laparoscopy after a careful selection, excluding subjects with previous either multiple or major surgery as well as neoplastic diseases. Such results need future confirmations from prospective randomized studies.

Initial experience with laparoscopic adrenal surgery in children: is endoscopic surgery recommended and safe for the treatment of adrenocortical neoplasms?

Through a review of 83 cases reported in literature, including our experience of two successful right laparoscopic adrenalectomies performed in a 3-year-old girl for androgen-secreting adenoma and in a 9-year-old male for pheochromocitoma, we have anaIyzed the indications, the techniques and the results of laparoscopic or retroperitoneoscopic adrenalectomy in children. Nineteen pheochromocytomas, 18 neuroblastomas, 15 adenomas, 12 ganglioneuromas, 9 hyperplasias, 2 carcinomas, 1 teratoma and 1 adrenogenital syndrome have been treated with excellent results (follow-up 1 month to 4 years) with no evidence of recurrence. The age range is from 1 month to 16 years with an equal female/male ratio. The tumor size range from 10 mm to 80 mm with approximately a mean of 40 mm. Sixty-three laparoscopies of which 54 lateral and 9 anterior have been performed versus 14 posterior retroperitoneoscopies. Regarding right adrenalectomy, 29 were laparoscopic and only 2 retroperitoneoscopic. With regards to left adrenalectomy, 23 were laparoscopic and 9 retroperitoneoscopic. Looking at bilateral lesions, these tumors were approached laparoscopically in 6 cases alternating both sides and 1 retroperitoneoscopically (this case was already operated on the other side). The operative time ranged from 25 minutes in newborn to 320 minutes in bilateral cases with an average of 120 minutes. Conversion rate is higher in retroperitoneoscopy (30%) (4 cases out of 13), than laparoscopy (6%) (4 cases out of 63). Specifically, for right retroperitoneoscopic adrenalectomy conversion rate was 100% (2 cases out 2), for left retroperitoneoscopic adrenalectomy 22.2% (2 cases out 9), for right laparoscopic adrenalectomy 6.8% (2 cases out of 29) and for left laparoscopic adrenalectomy 8.6% (2 cases out of 23). Only in 1 case were blood transfusions requested. Hospital stays ranged from 35 hours to 17 days with an average of 4 days. In conclusion the indications of endoscopic adrenalectomy in children are not different from those of traditional surgery and the well-known advantages of laparoscopic adrenal surgery should be applied to pediatric patients. It seems that there is no age and tumor size limits for a well-trained surgical team. Lateral transperitoneal approach is the most utilized with the child positioned in 90-degree flank decubitus. Laparoscopy is undoubtly preferred for right adrenalectomy (93% of cases), while for left adrenalectomy retroperitoneoscopy has been used in 39% of the cases. Considering the conversion rate and on the basis of our experience with adults, we recommend laparoscopic adrenalectomy for both right and left adrenal lesions, but we think that the pediatric surgeon should feel free to choose the approach in which he/she is more skilled. However, the best surgical result will be achieved if the pediatric and adult surgeon collaborate with their different experiences. Lastly, we suggest the use of new technological devices such as Ultracision Harmonic Scalpel which was a critical factor in our two successful right adrenalectomies.

Laparoscopic decapsulation of a large epidermoid splenic cyst in a child using the UltraCision LaparoSonic Coagulating Shears.

Splenic cysts are rare in pediatric surgery. Congenital epidermoid cysts are exceptional representing only 2.5% of all splenic cysts in childhood. Nowadays, considering the short- and long-term complications of splenectomy in children, the management of epidermoid cyst consists of partial splenectomy or decapsulation of the cystic wall. To our knowledge, the case reported in this article describes the first successful laparoscopic decapsulation of an epidermoid splenic cyst in an 10-year-old child using the UltraCision LaparoSonic Coagulating Shears (LCS). Follow-up at six months confirms no recurrence. Laparoscopic splenic decapsulation provides minimal access and small surgical trauma for treating the cyst while preserving splenic function. The use of UltraCision LCS makes the laparoscopy safely, expeditiously, with minimal blood loss and short hospital stay.

[New issues in surgery of adrenal pheochromocytoma]. / Nuove problematiche in tema di chirurgia del feocromocitoma a sede surrenalica.

The adrenal pheochromocytoma still arouses great interest among the experts. The Authors give here a report of a study carried out on the personal case history of 32 patients and the concerning literature. A correct clinical and diagnostic approach is important to detect, at a preoperative level, the benign forms from the malignant ones (10-15% of cases according to literature) and the polyendocrine syndromes (21% of our series). Video-laparoscopy technique is recommended in pheochromocytomas surgery, mainly in asymptomatic and incidental forms and in all benign symptomatic forms less than 5 cm in size. At least, uni- or bilateral adrenalectomy associated with total thyroidectomy is also suggested in case of a polyendocrine syndrome.

[Videolaparoscopic adrenalectomy in Conn syndrome. Analysis of 39 case observations]. / La videolaparosurrenectomia nella sindrome di Conn. Analisi di 39 casi osservati.

The authors retrospectively analyse 39 patients affected by Conn's syndrome, which have been observed since 1985, and discuss the results of surgical approach using the new technologies. In particular, the introduction of laparoscopy, technique that has been applied almost exclusively since the last seven years, has revealed being the "gold standard" for the surgical treatment of this disease. The adrenal underlying lesions are indeed almost always monolateral, small in size and present very rarely malignancy in their biological behaviour. Furthermore, the authors, although lacking of personal experience, propose the possibility of a more conservative treatment of the adrenal lesions with a simple "enucleation", whose feasibility also in laparoscopy has recently been shown by some authors. Anyway, the Authors believe that this technique of a partial adrenalectomy could be chosen in selective cases of bilateral adenomas or hyperplasia or in those lesions which are placed in an easily accessible peripheral site.

Laparoscopic adrenalectomy. Personal experience in 78 patients.

Laparoscopic adrenalectomy has proved to be the technique of choice for the treatment of benign pathologies of the adrenals and also for the treatment of isolated adrenal metastases, especially arising from lung tumor, but it shouldn't be performed for primitive adrenal carcinoma. The harmonic scalpel is very useful for laparoscopic adrenalectomy showing a significant reduction in operative time. The Authors retrospectively investigated 78 laparoscopic adrenalectomies performed from April 1995 to April 2000 using a transperitoneal approach with the patient on a lateral position as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals also by means of new technological devices as the Harmonic scalpel. The 78 laparoscopic adrenalectomies were performed in 70 cases for benign neoplasms: incidentalomas 24, Cushing's disease 16, Conn's disease 20, pheochromocytomas 9, myelolipoma 1. In the remaining 8 patients laparoscopic adrenalectomy was performed in 7 cases for isolated adrenal masses (5 metastases, 2 adenomas) in neoplastic patients, and in 1 patient for a preoperatively diagnosed adrenal carcinoma. Patients operated for functioning neoplasms had all remission or improvement of symptoms and humoral parameters; patients operated for isolated adrenal metastases showed this survival: 3 patients 3 years asymptomatic and disease free, 1 patient 18 months, and 3 patients are still alive and healthy after 6-12-15 months. A fast onset of local recurrence was seen in a patient operated for a preoperatively diagnosed adrenal carcinoma. We analyzed the operating time dividing the patients in three groups: a) 14 patients operated in the first semester of 1998 when we completed the training curve (average operative time 120.7 minutes); b) 14 patients operated from 1998-1999 (average operative time 118 minutes); c) the last 14 patients (operated from December 1999 to April 2000) where surgery was performed using the Harmonic scalpel (HS) (average operative time 94 minutes). The analysis of the average operative time comparing groups B and C using T-Student Test showed a significant reduction (p = 0.004). The morbility rate was 2.6%, mortality 1.3%, and a conversion rate of 2.6%. Laparoscopic approach results to be an extremely reliable procedure also for the treatment of incidentalomas up to 4-5 cm in which the incidence of adrenal carcinoma is about 13%. Doubts may yet result for the treatment of adrenal carcinomas preoperatively diagnosed. When laparoscopic adrenalectomy in performed using HS the operative time is significantly reduced and surgery is easier.