Mineralocorticoid Receptor Antagonists and Clinical Outcomes in Primary Aldosteronism: As Good as Surgery?

Primary aldosteronism (PA) is detected with increasing frequency in hypertensive patients and is associated with excess cardiovascular, renal, and metabolic complications. For these reasons, appropriate choices for treatment of this endocrine condition are mandatory. Adrenalectomy is safely performed in PA patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone secretion. AVS, however, is a complex procedure and even among worldwide referral centers there are substantial discrepancies for interpretation of results. Also, in the majority of PA patients with lateralized aldosterone secretion, hypertension may persist after adrenalectomy requiring use of additional antihypertensive agents. Treatment with mineralocorticoid receptor antagonists (MRAs) is currently recommended for PA patients with bilateral adrenal disease, but these agents effectively decrease blood pressure also in patients with unilateral disease, although concern remains for possible sex-related side effects. Prospective studies indicate that MRAs have therapeutic values comparable to surgery in the long-term, inasmuch as they effectively correct metabolic abnormalities and subclinical organ damage and reduce the risk of cardiovascular events and renal disease progression. This article overviews the clinical outcomes obtained in patients with PA with use of MRAs.

Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism.

Recent evidence indicates a greater frequency of primary aldosteronism (PA) among patients with hypertension than the previously accepted prevalence. PA was once considered a relatively benign form of hypertension associated with low incidence of organ complications. Recent views, however, suggest that long-term exposure to increased aldosterone levels might result in cardiovascular, renal, and metabolic sequelae that occur independently of the blood pressure level. Cross-sectional comparisons with patients with essential hypertension have demonstrated that patients with PA are at higher risk of cardiovascular events, have more frequent left ventricular hypertrophy and diastolic dysfunction, have greater urinary albumin losses as a marker of a hemodynamic intrarenal adaptation, and are insulin resistant. Some of these findings have been corroborated by the results of short-term, follow-up studies where it was shown that unilateral adrenalectomy or treatment with mineralocorticoid receptor (MR) antagonists are effective in correcting hypertension and hypokalemia. Normalization of blood pressure and correction of hypokalemia, however, are not the only goals in managing PA and effective prevention of organ complications is mandatory in these patients. The relative efficacy of adrenalectomy and MR antagonists, in the long-term, on the cardiovascular, renal, and metabolic outcomes still needs evaluation, being the aldosterone-induced tissue damage the main factor that could justify the cost of increasing efforts in screening of disease and differentiation of subtypes. In this narrative review, we summarize the results obtained with either surgical or medical treatment of PA and outline the findings of long-term, prospective studies on the effects of treatment on cardiovascular and renal outcomes and on insulin sensitivity.

Surgery in hepatic and extrahepatic colorectal metastases.

Extrahepatic disease (EHD) has been considered a contraindication to hepatectomy. Over the last few years, some series reported interesting 5-year survival rates after resection with hepatic colorectal metastases and EHD free margins. Between August 1989 and October 2005, 116 patients underwent liver resection for colorectal metastases at Surgical Department of the University of Udine, Italy. Among these, we reviewed the data of 5 patients affected by EHD. In 3 patients there were also an anastomotic recurrence of the primary tumor, in 3 patients diaphragm was infiltrated by contiguous liver metastases. We performed in all the patients minor liver resections. We have associated the radiofrequence ablation of a lesion not surgically resectable with liver resection in one case. The surgical procedure was always considered as curative. We observed no case of operative mortality. The mean survival of the entire cohort is 23.2 months (range 4-42 months). Our study, even if based upon a limited number of patients, supports the thesis that extrahepatic disease in patients affected by colorectal cancer with hepatic metastases should not be considered as an absolute contraindication to liver resection especially for the cases in with local radical cure exeresis is achievable.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma.

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.

Preoperative chemoradiotherapy in cancer of the thoracic esophagus.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

The impact of splenic weight on laparoscopic splenectomy for splenomegaly.

BACKGROUND: Enlarged spleens increase the technical difficulties associated with laparoscopic splenectomy (LS). The aim of this study was to analyze the impact of splenic weight on the results of LS. METHODS: We performed a prospective analysis of 20 LS for splenomegaly and 40 LS for normal spleen in terms of intraoperative and early postoperative outcome. RESULTS: Patients with splenomegaly had longer operative times and higher conversion and transfusion rates than those with normal spleens. Patients with spleens weighing < 2000 G experienced less blood loss, fewer conversions, and a shorter postoperative hospital stay than those with spleens > 2000 g. No differences-except for the longer operative time-were observed between normal-sized spleens and those weighing < 2000 G. CONCLUSIONS: LS for splenomegaly is feasible for experienced laparoscopic surgeons. For spleens weighing < 2000 G, the outcome was comparable to that of normal spleens, whereas LS for spleens >2000 g was associated with a higher conversion rate, greater blood loss, a longer hospital stay, and increased morbidity.

Distant metastases from cervical esophagus cancer.

Cancer of the cervical esophagus has a poor prognosis in relation to stage. Correct staging is thus essential in order to establish the prognosis and the treatment program. Distant metastases can involve the lymph nodes (mediastinal and celiac lymph nodes) or they can be extranodal visceral types. Correct lymph node staging can be performed with esophageal endoscopic ultrasonography, computed tomography (CT) scan and, currently, with positron emission tomography (PET) and minimally invasive surgery. For hematogenous metastases, CT scan and PET are mainly used, as well as minimally invasive surgery, with the eventual aid of intraoperative ultrasonography.

Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients.

BACKGROUND: Aggressive hepatocellular carcinoma (HCC) complicates frequently hereditary hemochromatosis, a disease for which a strong candidate gene, named HFE, has recently been identified. Patients with HCC who are heterozygotes for mutations in the HFE gene might have distinct features and a distinct disease course. METHODS: The presence of the 2 mutations associated with hereditary hemochromatosis (C282Y and H63D) was sought by restriction fragment length polymorphism in 61 cirrhotic patients (46 males and 15 females) who underwent resection for HCC at a single institution. RESULTS: There were 4 heterozygotes for the C282Y mutation and 6 homozygotes + 20 heterozygotes for the H63D mutation, with no compound heterozygotes. Carriage of >/= 1 HFE mutated allele was significantly more frequent in HCC patients than in 149 control subjects (44% vs. 29%, P = 0.005). Among C282Y heterozygotes, 3 of 4 were female, compared with 12 of 57 wild-type carriers (P = 0.015); no gender distribution existed among patients carrying H63D alleles (6 of 26 vs. 9 of 35, P = 0.813). Survival was longer for patients with wild-type HFE than for those with mutated HFE (67% vs. 22% at 3 years; hazard ratio = 0.42, 95% confidence interval = 0.21-0.80) (P < 0.01). The negative effect on survival that resulted from possessing >/= 1 HFE mutated allele was maintained even after adjustment for gender, age, presence of tumor capsule, presence of comorbid factors, Okuda stage, Edmonson grading, and number of lesions (P = 0.01). CONCLUSIONS: Testing for HFE mutations may help identify HCC patients with dismal prognoses for whom surgical resection may not represent the best treatment option.

[Echolaparoscopy in the staging of abdominal neoplasms. Prospective study]. / L'ecolaparoscopia nella stadiazione delle neoplasie addominali. Studio prospettico.

OBJECTIVE: To evaluate the sensitivity, specificity, positive and negative predictive value and influence on surgical strategy of laparoscopy and laparoscopic ultrasound on staging of abdominal malignancies. MATERIAL AND METHODS: Prospective evaluation of laparoscopic ultrasound staging, according to the TNM classification, of 80 consecutive cases of abdominal malignancies in terms of sensitivity, specificity, positive and negative predictive value and influence on surgical strategy. Pathologic examination of final surgical specimens or laparoscopic biopsies was used as control. RESULTS: Laparoscopic ultrasound evaluation was carried out successfully in 95% of cases with no mortality and morbidity. Twenty one out of 76 patients (28%) had their stage changed based on laparoscopic ultrasound findings. Unnecessary laparotomy was avoided in 11 cases (14%) due to evidence of advanced disease at laparoscopic ultrasound. For pancreatic cancer laparoscopic ultrasound was more sensitive for TNM, specificity was higher just for nodal evaluation. For liver tumor laparoscopic staging revealed more sensitive for N and M evaluation. Laparoscopic ultrasound staging had low specificity and sensitivity for T evaluation, while it was more sensitive and specific than clinical staging for nodal and distant metastasis assessment respectively for gastric and colon cancer. CONCLUSION: Laparoscopic ultrasound staging is a safe, feasible and effective staging tool for several abdominal malignancies. The introduction of laparoscopic ultrasound probes overcomes the lack of tactile sensation proper of laparoscopy, allowing precise evaluation of both solid and deeply located abdominal structures. The use of laparoscopic ultrasound staging may help to reduce the number of unnecessary laparotomies.

Primary lymphoma of the liver: a case report and review of the literature.

Primary lymphoma of the liver (PLL) is a rare disease and estimation of the real number of cases may be difficult because strict diagnostic criteria for the definition of a primary lesion are quite often not followed. We report here on a case of a patient affected by PLL who underwent successful surgical resection of the lesion followed by chemotherapy and autologous bone marrow transplantation. The patient is alive and disease free 62 months after resection.

[Laparoscopic versus laparotomic adrenalectomy: preliminary experiences]. / Surrenectomia laparoscopica versus laparotomica. Esperienze preliminari.

The authors report their experience about laparoscopic surgery in the treatment of adrenal tumours. Three laparoscopic right adrenalectomies were performed. From a comparison with five open adrenalectomies, microinvasive surgery is more advantageous than traditional management: recovery is earlier, incisions are smaller, post-operative discomfort is less, physiologic functions recover in a short time, return to full professional activity in one week.

[Surgical treatment of liver metastases of breast carcinoma. Our experience]. / Trattamento chirurgico delle metastasi epatiche da carcinoma mammario. Nostra esperienza.

The authors report their experience in the surgical treatment of breast cancer liver metastases. Although with a restricted number of cases (4 patients), the short-term results are satisfactory; this is in agreement with the literature. The survival of those patients treated with a loco-regional approach to metastases (chemotherapy and surgery), is longer than one obtained using systemic chemotherapy. This is still an open question requiring further experience.

[Ultrasonography-guided percutaneous needle biopsy with large needle versus surgical biopsy in the diagnosis of breast lesions]. / Agobiopsia percutanea ecoguidata con ago grosso vs biopsia chirurgica nella diagnosi delle lesioni mammarie.

The authors report their experience on percutaneous large core biopsy with standard needle in the diagnosis of breast lesions. This method, that has the same advantages of open biopsy, allows a better cytological examination, prevent sequelae of surgery and lower costs.

[Arterio-portal fistula. Report of a case and review of the literature]. / Fistole artero-portali. Segnalazione di un caso e revisione della letteratura.

Mesenteric arteriovenous fistulas or arterioportal fistulas (APF) are rare and mostly secondary to penetrating abdominal wounds. A rare case of APF presenting 2 years later a blunt abdominal trauma has been reported. On the basis of a review of the literature (65 cases) the etiology, clinical findings, diagnostical aspects and the results of conservative and surgical treatment have been analyzed.

[Medullary carcinoma of the breast. A review of the literature and a report of the authors' own cases]. / Carcinoma midollare della mammella. Revisione della letteratura e presentazione della casistica personale.

Experience with 5 cases of medullary carcinoma of the breast is reported. Reviewing the literature, medullary carcinoma appears to have a better prognosis than infiltrating ductal carcinoma so the proper surgical approach is represented by conservative procedures for lesions < 3 cm with no more than 3 nodes involved. Chemotherapy and radiotherapy don't seem to improve the survival rate.

Simultaneous pancreas kidney transplantation: initial experience of the Emory University transplant service.

The successful replacement of islet tissue by pancreas transplantation appears to be beneficial in the early course of those uremic diabetic recipients who receive a simultaneous renal transplant. The long-term advantages of SKP transplantation remain to be determined, however, current improvement in patient and graft survival following SPK and the difficulties thus far reported in islet cell transplantation have renewed clinical interests in SPK, PAK and PA transplantation. In our experience, pancreas transplantation has been a challenging technical, immunological and physiological endeavor which was well received by our patients despite the initial problems and complications we and they encountered. Notwithstanding extensive preparation, our team experienced a "learning curve" and we present many of the lessons we learned. This knowledge has aided our transplant team in the successful management and avoidance of these complications and other inherent problems associated with SKP transplantation in subsequent patients.

Chilaiditi's syndrome as a surgical and nonsurgical problem.

Hepatodiaphragmatic interposition of the intestine is a rare anomaly (0.025 to 0.28 percent of the general population) described by Chilaiditi in 1911 and often believed to be of irrelevant clinical interest. To the contrary, recent studies stated that this syndrome is a potential source of abdominal problems requiring emergency or elective operation. From a retrospective analysis of records since 1976, four instances of Chilaiditi's syndrome have been found (three males and one female). Interposition of the proximal transverse colon was found in three patients and the small intestine in one patient. The findings of plain roentgenograms of the chest were determinants for diagnosis in three patients. In one patient, a barium meal was given to obtain a better definition. Two patients were admitted for malignant neoplasms (metastatic carcinoma of the breast, carcinoma of the gastrointestinal tract and cirrhosis of the liver) and died within a few months. The other two patients complained of abdominal pain. Patient No. 4 had gastric volvulus. Chilaiditi's syndrome was diagnosed intraoperatively in that patient and a surgical treatment with hepatopexy was performed, by suturing the falciform, the coronaria ligament and the anterior margin of the liver to the diaphragm with interrupted absorbable stitches. After a two year follow-up evaluation, this patient is as well as the patient who underwent medical therapy. Volvulus of the stomach, as was found in Patient No. 4, is an unusual condition and, to our knowledge, the patient is the second reported instance.

[An aneurysm of the extracranial carotid. A report of an interesting clinical case]. / Aneurisma della carotide extracranica. Descrizione di un caso clinico interessante.

One case of extracranial carotid artery aneurysm observed is reported. This uncommon and interesting vascular disorder is still under discussion even if the present tendency is to treat it actively by reconstructive surgical procedures that make it possible to avoid the natural aneurysm complications with a low risk of postoperative neurological lesions.

[Hemocholecyst: a rare cause of hemoperitoneum]. / Emocolecisti: rara causa di emoperitoneo.

A rare case of haemoperitoneum due to gallbladder rupture with intraluminal bleeding is reported. The importance of a coagulopathy in the etiology of the disease is pointed out: in the present case it was related to cirrhosis and anticoagulant treatment during dialysis sessions.

[Tumors of the carotid glomus (chemodectomas)]. / I tumori del glomo carotideo (chemodectomi).

Two cases of carotid body tumor (chemodectomas) have been reported and at this regard the international literature reviewed. Concerning the diagnosis selective angiograms represent the investigation of choice in clinical assessment and planning operative approach. Doppler-ultrasound results particularly useful in the follow up of patients after surgery. With advances in vascular technique, complete excision of the tumor has become possible and is now associated with minimal morbidity and mortality. Survival rate of resected patients is equivalent to that for sex age matched control subjects.