Prevalence and Clinical Outcome of CYP21A2 Gene Mutations in Patients with Nonfunctional Adrenal Incidentalomas.

Adrenal tumors, discovered incidentally in approximately 4.5% of imaging procedures, are known as adrenal incidentalomas. Nonclassic congenital adrenal hyperplasia, mild form of 21-hydroxylase deficiency, may lead to the development of adrenocortical tumors. The aim of the study was to evaluate prevalence of the most common nonclassic mutations of CYP21A2 gene in patients with adrenal incidentalomas and investigate possible relationship with clinical outcome. One hundred adult patients with such lesions were enrolled. Clinical, imaging and biochemical evaluation were performed to rule out hormonal overproduction or potential malignancy. All subjects and a control group of 100 neonates were genotyped for P30L, P453S, and V281L mutations of CYP21A2 gene using direct sequencing. Clinical and imaging features as well as hormone levels were analyzed. Heterozygous CYP21A2 gene mutations were detected in 8 subjects but not in the neonates. Thus, the risk of carrying mutant allele was significantly higher in subjects with adrenal tumors (OR=8.7; 95% CI=2.23-389.56; p=0.003). Mean concentrations of renin, basal, and stimulated 17-hydroxyprogesterone were higher and ACTH was lower in the carriers than in the remaining subjects. Furthermore, the carriers had higher incidence of hypertension (100 vs. 52.1%, p=0.008) and diabetes (50 vs. 11.9%, p=0.003). ACTH-stimulated 17-hydroxyprogesterone levels varied widely among the carriers. In summary, prevalence of P30L, P453S, and V281L mutations of CYP21A2 gene is increased in patients with adrenocortical tumors. In these subjects, carrying the analyzed mutant alleles may increase the risk of diabetes and hypertension. ACTH-stimulation test does not satisfactorily predict presence of heterozygous CYP21A2 mutations in patients with adrenal tumors.

Pancreatoduodenectomy with subtotal stomach-preserving and uncut Roux reconstruction.

BACKGROUND/PURPOSE: Pylorus-preserving pancreatoduodenectomy (PD) has become the therapy of choice for resectable tumors located in the head of the pancreas and periampullary region. In addition, a distal gastrectomy may still be required for tumors located in the dorsal part of the pancreatic head or when there is evidence of proximal duodenal invasion. This may lead to postoperative complications, including gastric dumping, marginal ulceration, and bile reflux gastritis. This study reports on the postoperative course following subtotal stomach-preserving PD with the uncut Roux reconstruction diverting biliary and pancreatic secretions from the gastric remnant. METHODS: A technique combining subtotal stomach-preserving PD with the uncut Roux reconstruction was applied in 10 patients. The postoperative clinical follow-up data are reviewed, and clinical criteria of biliary gastric reflux and gastritis were evaluated. RESULTS: The postoperative course was uneventful in 4 patients and complicated in 6 patients. Delayed gastric emptying occurred in 3 patients. No deaths occurred in the postoperative period. One patient suffered from occasional nausea with abdominal discomfort for which endoscopy and cholescintigraphy were performed. Endoscopy confirmed complete occlusion of the afferent jejunal limb and showed marginal ulceration within the gastrojejunal anastomosis. Cholescintigraphy showed signs of enterogastric reflux. The check-up endoscopy following typical antisecretory therapy revealed complete ulcer healing. Four patients died of tumor recurrence 6, 7, 8, and 12 months following surgery. CONCLUSION: This pilot study suggests that the uncut Roux reconstruction may represent a good alternative to gastrointestinal reconstruction following PD. Further studies including the determination of intragastric bile acid concentration and radionuclide isotope scanning in a larger number of patients are warranted.

Administration of a recombinant factor Vlla in patients undergoing liver transplantation for fulminant hepatic failure.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with profound clotting disturbances leading to the risk of a major blood loss during orthotopic liver transplantation (OLT). Application of a recombinant factor VIIa (rVIIa) that promptly corrects clotting abnormalities remains controversial in the OLT setting. We conducted a retrospective analysis of the effect of rVIIa on the prothrombin time (PT) and other perioperative parameters in patients transplanted for FHF in our center. MATERIALS AND METHODS: Nineteen consecutive patients (9 males/10 females) of overall mean age of 33 +/- 13 years underwent the procedure due to: Wilson's (n = 8), non-A-non-B hepatitis (n = 6) or Amanita phalloides toxicity (n = 5). All subjects received rVIIa at a mean dose of 54 +/- 16 microg/kg body weight at 10 minutes before the skin incision. The PT was measured at 15 minutes and 12 hours after injection. Data were analyzed with StatView program with P < .05 considered significant. RESULTS: Rapid correction of PT was observed in all patients: the mean PT before injection was 37 +/- 14 versus 14 +/- 3 after 15 minutes (P < .0001). Twelve hours after the injection the PT was 19 +/- 5 (P < .0001 vs before injection and P < .0007 vs 15 minutes after injection). Two patients died at 1 and 4 days after OLT. Mean red blood cell requirement was 5 +/- 4 U and fresh frozen plasma was 11 +/- 5 U. The mean operative time was 527 +/- 126 minutes and intensive care unit stay 8 +/- 9 days. None of the patients developed thromboembolic complications. CONCLUSION: Administration of rVIIa caused a rapid improvement in the PT shortly after injection. It was safe and not associated with any thromboembolic events in our series.

Immunosuppression with low-dose daclizumab in liver transplant recipients with impaired kidney function: a single-center experience.

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNI) may exert detrimental effects, particularly in orthotopic liver transplantation (OLT) patients with impaired kidney function. Immunosuppression with daclizumab permits delayed introduction of CNI, and may be preferred for patients with kidney dysfunction. This retrospective analysis of our experience using daclizumab was performed among patients who underwent transplantation with impaired kidney function. METHODS: We analyzed 168 patients. A serum creatinine (Cr) level >1.5 mg/dL was the indication for a protocol with low-dose daclizumab (50 mg intravenous [IV], day 0 and day 4), mycophenolate mofetil (MMF; 500 mg twice daily IV/orally), and tapering doses of prednisolone from day 0 after OLT. CNI were introduced at day 4-15 after OLT. Patients with a Cr level <1.5 mg/dL received immunosuppression with CNI+MMF+steroids or CNI+steroids. RESULTS: Fourteen patients fulfilled the criterion for daclizumab immunosupression. Their Cr and creatinine clearance (CrCl) values at OLT were 2.85 +/- 1.22 mg/dL and 19 +/- 11 mL/min, respectively. In the remaining 154 patients, Cr and CrCl results were 0.88 +/- 0.3 mg/dL and 107 +/- 82 mL/min, respectively. At discharge, the daclizumab group showed Cr and CrCl estimates of 0.97 +/- 0.45 mg/dL and 86 +/- 34 mL/min (P < .0001 for both, when compared with prior to OLT). Both Cr and CrCl levels at discharge were not different from those values of patients who underwent transplantation with normal kidney function. The incidence of acuterejection was 14% in the daclizumab group and 18% in the other recipients (P = not significant [NS]). CONCLUSIONS: Immunosuppression with low-dose daclizumab and delayed introduction of CNI was safe and did not increase the risk of an acute rejection episode, thus offerring an excellent therapeutic option for patients who undergo transplantation with impaired kidney function.

Reduction of biliary complication rate using continuous suture and no biliary drainage for duct-to-duct anastomosis in whole-organ liver transplantation.

Biliary complications (BC) following orthotopic liver transplantation (OLT) are related to various factors including surgical technique and use of biliary drains for a duct-to-duct (DD) anastomosis. Herein we have reported the influence of changes in surgical technique on BC following OLT in our center. From February 2002 to February 2007, we performed 101 whole-organ OLT with a DD anastomosis in 99 adults, of whom we analyzed 84 subjects. We excluded recipients who died within 30 days of OLT without any evidence of BC and 1 patient with a biliary stricture secondary to a hepatic artery thrombosis. Until late 2004, a DD anastomosis with interrupted sutures over an external biliary drain (DD/BD) was performed in 35 patients (Group I). Subsequently, no biliary drain was used for the DD anastomosis (DD/non-BD), using a continuous suture in 49 patients (Group II). The DD anastomosis with interrupted sutures over a biliary drain was associated with a higher incidence of both total (31% vs 8%; P = .008) and late BC (>30 days; 20% vs 2%; P = .008) with a trend toward more leaks (17% vs 4%; P = .06). All biliary leaks in patients with DD/BD reconstruction occurred at the exit site of the biliary drain following its removal. No significant differences were observed when we compared the incidence of biliary strictures and the necessity for surgical intervention. One patient died due to a BC. Our results indicated that a DD anastomosis performed with a continuous suture technique and no external biliary drainage reduced the incidence of BC after whole-organ OLT.

Vascular complications following adult piggyback liver transplantation with end-to-side cavo-cavostomy: a single-center experience.

BACKGROUND: Vascular complications remain a significant cause of morbidity, graft loss, and mortality following orthotopic liver transplantation (OLT). These problems predominantly include hepatic artery and portal vein thrombosis or stenosis. Venous outflow obstruction may be specifically related to the technique of piggyback OLT. MATERIALS AND METHODS: Between February 2002 and February 2009, we performed 200 piggyback OLT in 190 recipients. A temporary portacaval shunt was created in 44 (22%) cases, whereas end-to-side cavo-cavostomy was routinely performed for graft implantation. Pre-existent partial portal or superior mesenteric vein thrombosis was present in 17 (12%) cirrhotics in whom we successfully performed eversion thrombectomy, which was followed by a typical end-to-end portal anastomosis. The donor hepatic artery was anastomosed to the recipient aorta via an iliac interposition graft in 31 (16%) patients. RESULTS: The 14 (7%) vascular complications included hepatic artery thrombosis (n = 5), hepatic artery stenosis (n = 3), aortic/celiac trunk rupture (n = 2), portal vein stenosis (n = 2), and isolated left and middle hepatic venous outflow obstruction (n = 1). There was also 1 case of arterial steal syndrome via the splenic artery. No patient experienced portal or mesenteric vein thrombosis. Therapeutic modalities included re-OLT, arterial/aortic reconstruction and splenic artery ligation. Vascular complications resulted in death of 5 (36%) patients. CONCLUSION: Our experience indicated that piggyback OLT with an end-to-side cavo-cavostomy showed a low risk of venous outflow obstruction. Partial portal or mesenteric vein thrombosis is no longer an obstacle to OLT; it can be successfully managed with the eversion thrombectomy technique.

Outcome of emergency liver transplantation including mortality on the waiting list: a single-center experience.

Patients with irreversible fulminant hepatic failure (FHF) as well as recipients with primary graft nonfunction (PNF) and early hepatic artery thrombosis (HAT) die unless they undergo emergent liver transplantation (OLT). Therefore, they have the highest priority in organ allocation systems. Herein we describe our initial experience with 18 emergency among 103 OLT procedures performed in 99 adults from February 2002 through February 2007. Their diagnoses were FHF (n = 16), PNF (n = 1), and early HAT (n = 1). Ten subjects (56%) underwent emergency OLT after a mean 1.6 (range, 1 to 4) days after listing, whereas 8 (44%) patients died while awaiting a graft for a mean of 5.9 days (range, 2 to 17). All the transplants were performed according to the piggyback technique with routine preoperative use of intravenous recombinant factor VIIa (rVIIa) to control the coagulopathy, which resulted in significant (P < .0001), prompt correction of prothrombin time from a mean of 61 (range, 22 to 300) to 14 (range, 11 to 22) seconds at 15 minutes after drug administration. A mean of 4 (range, 0 to 14) units of RBC and 9 (range, 3 to 18) units of fresh frozen plasma were transfused during the procedure. Eight (80%) transplanted patients are alive in good condition with normal liver function at a mean of 18 (range, 4 to 36) months follow-up. Two patients died in the early postoperative period after massive aortic bleeding and biliary sepsis. In summary, only 56% of patients requiring emergency OLT received grafts achieving good medium and long-term survivals, which was significantly lower compared with Western European centers where this proportion reaches 90%. This outcome could be improved by international organ-sharing arrangements for emergency transplantation or living donation alternatives.

Liver transplantation for fulminant hepatic failure without venovenous bypass and without portacaval shunting.

Preservation of the caval vein during liver transplantation (OLT) has gained wide acceptance but portosystemic bypass or temporary portocaval shunt is still believed to be indicated in patients with fulminant hepatic failure. Herein we have described our initial experience with piggyback OLT without venovenous bypass and without portocaval shunting in five such patients. Division of the portal vein was always delayed until the native liver was completely dissected off the caval vein. The donor hepatic artery was anastomosed to the recipient aorta via an iliac interposition graft placed in the supraceliac position in two and at an infrarenal site in three patients. The ahepatic phase urinary output was low in the two patients in whom we applied supraceliac cross-clamping of the aorta. The mean ahepatic phase was 53 (45 to 67) minutes in four recipients who remained hemodynamically stable throughout surgery and prolonged to 5 hours in one patient due to a complicated supraceliac aortic anastomosis. Its repair resulted in hemodynamic instability, multiorgan failure, and death at 4 days following OLT. Four (80%) patients are alive in good condition with normal liver function after a mean of 12 (5 to 25) months of follow-up. In summary, liver transplantation for fulminant hepatic failure may be safely performed without venovenous bypass and without temporary portocaval shunting if the ahepatic phase is minimized and portal flow to the liver maintained up to the moment of hepatic excision. Arterial anastomosis with the supraceliac aorta prolongs the ahepatic phase and may impair kidney function: therefore, it should be avoided in these patients.

Rapid correction of prothrombin time after low-dose recombinant factor VIIA in patients undergoing orthotopic liver transplantation.

Orthotopic liver transplantation (OLTx) is associated with a major risk of blood loss resulting from portal hypertension, collateral circulation, and clotting disturbances. Application of a recombinant factor VIIa (rFVIIa) has been reported to promptly correct clotting abnormalities reducing the risk of intraoperative bleeding. This study included 8 patients who underwent OLTx for end-stage liver cirrhosis, with protrombin times (PT) exceeding the upper limit of normal by more than 4 seconds before surgery. All subjects were administered a small single intravenous dose of rFVIIa [mean 68.37 microg/kg body mass (range, 32.88-71.64)] 10 minutes prior to the skin incision. The PT was then measured 15 minutes later, following graft reperfusion, and 12 hours since drug application. All patients showed rapid correction of PT within 15 minutes after injection (median PT before injection 20.25 seconds vs 11.5 seconds after injection, P <.0001). Following the reperfusion PT was found to be prolonged again. These values are not significantly differ from those before surgery and are comparable to PT values after reperfusion in patients who did not receive rFVIIa. None of the patients developed thromboembolic complications. In conclusion, lower than recommended dose of rFVIIa caused rapid improvement in the PT shortly after injection. After reperfusion PT became prolonged again, which may account for the lack of thromboembolic complications observed in this group of patients.

One hundred and ten consecutive uncomplicated retroperitoneal videoscopic adrenalectomies--Polish multicentre study.

AIM: The authors evaluate the effectiveness of videoscopic adrenalectomy (VA) for a variety of endocrine disorders. METHODS: One hundred and ten consecutive videoscopic adrenalectomies performed from October 1995 till December 2000 were reviewed and followed up for adequacy of surgical treatment in 2 surgical departments. There were 79 females and 31 males included in the study. The mean age was 48.0 years (range 23-71 years). Indications for the operations were: phaeochromocytomas (n=5), aldosterone-producing adenomas (n=19), cortisol-producing adenomas (n=10), Cushing's disease (n=3) and non-secreting tumours (n=72). RESULTS: There was no mortality and no morbidity both intraoperatively and in the postoperative course. In 8 cases conversion to open surgery was instituted - in 4 cases due to an unintended lesion of pertioneum without damage to the intraperitoneal organs. Mean operative time was 156 min (range 52-280 min), and estimated blood loss was 73 ml (range 20-300 ml). The average length of hospital stay was 2.9 days (range 2-7 days). None of the patients revealed either recurrence of hormonal hypersecretion or tumour mass in imaging studies during the follow-up period (range 1-34 months). CONCLUSION: 1. VA is recommended in patients with hormonally active tumours and in patients with benign adrenal masses of a diameter up to 6 cm. 2. VA is a safe and feasible procedure if performed by a team experienced in endocrine and endoscopic surgery. 3. VA is a procedure better than open adrenalectomy in management of small, non-malignant tumours because of the reduction of operative trauma.

Experience--the key factor in successful laparoscopic total extraperitoneal and transabdominal preperitoneal hernia repair.

To emphasize the importance of the experience of the operating team, we compared the two largest materials in the total extraperitoneal (TEP) and the transabdominal preperitoneal (TAPP) procedures in Poland. We performed 1225 procedures on 1110 patients (368 TEP and 809 TAPP). The experience of the operating teams measured by the mean number of procedures/surgeon was comparable. The mean operating time and hospitalization duration did not differ markedly. There was no procedure-related mortality. Intraoperative complications were infrequent. The ratio of early local complication (neuralgia, hematoma, and seroma) was slightly higher in the TEP group. We observed a higher recurrence rate following the TAPP procedure (2.84% vs 1.92%). However, after excluding the learning period this dropped markedly to much lower, comparable values (TEP: 0.98%; TAPP: 1.14%). In laparoscopic hernia repair the experience of the operating team seems to be more important than choice of technique (TEP vs TAPP).

Laparoscopic lymphocele drainage after renal transplantation.

The formation of a lymphocele in small pelvis following renal transplantation is a well-known complication. Although various non-operative methods are available, laparotomy with transperitoneal internal drainage has been the gold standard for the treatment of lymphoceles. In 1991, internal drainage of a renal transplant lymphocele was performed for the first time laparoscopically. Nine patients with symptomatic lymphoceles were treated using laparoscopic technique, between July 1995 and November 1999 in the Surgical Department of the District Hospital in Szczecin. In 8 patients, the laparoscopic approach was successful and no further therapy was required. In one case, the videoscopic procedure had to be converted to open surgery. Operative time ranged from 15 to 60 minutes. The postoperative course was uneventful in all nine cases. Laparoscopic method of treatment of a renal transplant lymphocele combines the efficiency of internal surgical drainage, with the minimal invasiveness of non-operative techniques. It reduces postoperative pain, shortens length of hospitalisation and convalescence, and has a similar recurrence rate to open surgery.

Influence of ureterovesical anastomosis technique on the incidence of vesicoureteral reflux in renal transplant recipients.

Urological complications of allogenic kidney transplantation include vesicoureteral reflux which can result in graft threatening urinary tract infection. To prevent this complication several ureterovesical anastomosis techniques have been developed. Authors present a comparison of three different techniques: extravesical without antireflux mechanism, extravesical Witzel-Lich with antireflux mechanism and intravesical Laedbetter-Politano with antireflux mechanism. 39 patients were selected randomly from a cohort of 420 allogenic kidney recipients (follow up time 10-147 months). All patients had voiding cystography and urine culture performed. The incidence of vesicoureteral reflux varied from 13.3% to 50%, depending on the anastomosis technique. No correlation between type of anastomosis and urinary tract infection was found.

[Comparisons of laparoscopic and classical adrenalectomy from personal material]. / Porównanie adrenalektomii laparoskopowej i klasycznej w materiale wlasnym.

Postoperative course in 12 patients which had laparoscopic adrenalectomy performed was compared with 8 underwent classic one in terms of operating time, blood loss, blood pressure recordings, C-reactive protein blood concentration, postoperative pain and hospital stay. The advantages of the laparoscopic approach have been stressed.

[Surgery for inguinal hernia from the extraperitoneal approach using laparoscopy--two years of personal studies]. / Operacja przepukliny pachwinowej z dostepu zewnatrzotrzewnowego z uzyciem laparoskopu--dwuletnie doswiadczenia wlasne.

From May 1995 to January 1997, 237 laparoscopic extraperitoneal inguinal hernia repairs were performed in Department of General Surgery of District Hospital in Szczecin. 197 patient had uni- and 20 bilateral inguinal hernia. The mean age of patients was 51 years. The average time of procedure and hospitalization was 38 min and 1.7 days respectively. Seven (3.2%) recurrences were observed in postoperative observation. As a conclusion, according to authors' achieved experience, one can say that the laparoscopic extraperitoneal inguinal hernia repair is in benefit both for patient and for surgeon.