Pathways and gene expression profiles in hepatocellular carcinoma.

Hepatocarcinogenesis is a process attributed to progressive genomic changes which alter the hepatocellular phenotype producing cellular intermediates evolving into clearly neoplastic cells (hepatocellular carcinoma, HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and this process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that develop genetic and chromosomal alterations. At the moment three main molecular pathways of liver carcinogenesis have been described and several attempts of genetic classification of HCC have been proposed. The definition of genomic and molecular changes which occur during the development of HCC should improve the classification and prognostis of liver tumors. The development of sorafenib and other new targeted developing therapies were rendered possible by the discovery and understanding of the molecular and genetic pathogenesis of hepatocellular carcinoma. Besides viruses, such as Hepatitis B virus (HBV) and Hepatitis C virus (HCV), may contribute to cancer development by several ways; however, additional factors, such as host immunity and chronic inflammation and host cellular mutations also play a role in the transformation process. The understanding of these pathways will in the future enable the clinician to focus the treatment patients with HCC and customize single or combination therapy.

The impact of single parathyroid gland autotransplantation during thyroid surgery on postoperative hypoparathyroidism: a multicenter study.

BACKGROUND: We compared the surgical outcomes in patients undergoing bilateral thyroid surgery with or without parathyroid gland autotransplantation (PTAT). METHODS: One thousand three hundred nine patients underwent surgery for treatment of various thyroid diseases at three Academic Departments of General Surgery and one Endocrine-Surgical Unit throughout Italy. A nonviable gland or difficulties in dissection of the parathyroid glands were encountered in 160 (13.7%) patients. The subjects were divided into two groups: (1) patients undergoing PTAT during thyroidectomy (n = 79) versus (2) control group (n = 81), patients not undergoing PTAT. RESULTS: Clinical manifestations occurred in 5.0% of PTAT patients and in 13.6% of control patients (P = NS). Total postoperative hypocalcemia was less among PTAT than control patients (17.7% and 48.1%, respectively; P = .0001). There was no significant difference between the two groups in terms of definitive hypocalcemia (0% vs 2.5% in PTAT and control, respectively). Transient postoperative hypocalcemia was less among PTAT than controls (17.7% vs 45.7%; P = .0002). PTAT was associated with decreased occurrence of hypocalcemia in the two subgroups of patients operated for benign euthyroid disease (P < .0001), as compared with the control group. CONCLUSIONS: PTAT is an effective procedure to reduce the incidence of permanent hypoparathyroidism. Transient hypoparathyroidism appears to not be influenced by PTAT. Moreover, we observed that damage to one parathyroid gland has more side effects (ie, transient hypocalcemia) among patients who were preoperatively at low rather than at high risk of postoperative hypocalcemia.

Hypoparathyroidism after total thyroidectomy.

The aim of the study is to describe the last advances (2000-2007) in the management of hypoparathyroidism secondary to total thyroidectomies. This systematic review was conducted according to recently presented guidelines on the argument. A comprehensive literature search was performed in August 2007 consulting PubMed MEDLINE for publications, matching the terms of hypoparathyroidism/ hypocalcaemia AND parathyroid glands, total thyroidectomy, thyroid surgery, postoperative complications, and risk factors. Hypoparathyroidism remains a frequent and challenging complication following total thyroidectomy. A meticulous surgical technique with an excellent anatomical knowledge of the neck compartment are mandatory to restrain its appearance. The application of lens magnification and of parathyroid glands autotransplantation (PTAT) during thyroid surgery contribute to preventing definitive hypoparathyroidism and also to decrease the postoperative incidence of transient hypocalcaemia. Consequently, the reduction of complications rate determines the decrease of the hospitalization length, costs, and patient discomfort due to a fear of clinical manifestations, and facilitates the return to work. The microsurgical approach and the PTAT are effective and easily learnable procedures, also adaptable in less favoured areas without additional cost. We believe that these performances represent a real aid in association with an operative strategy aiming always to the preservation of parathyroid glands in situ.

Second harmonic imaging improves trans-abdominal ultrasound detection of biliary sludge in 'idiopathic' pancreatitis.

BACKGROUND: Recently, biliary sludge has been strongly correlated with 'idiopathic pancreatitis'. It is often diagnosed by trans-abdominal ultrasonography, despite the low sensitivity of this investigation. New scanners, using second harmonic imaging, may improve the quality of the echographic picture. AIM: To verify the impact of this methodology on the detection of biliary sludge in patients with 'idiopathic' pancreatitis. METHODS: Fifty patients with 'idiopathic' pancreatitis observed over a 18-month period entered the study. Exclusion criteria were gall-bladder stones, polyps, clinical conditions related to biliary sludge development and haemolytic disorders. Patients were assessed blind by two operators using either conventional ultrasonography or second harmonic imaging. The parameters of diagnostic quality of both examinations were evaluated using, as the gold standard, microscopic examination of the gall-bladder content collected at endoscopy after cholecystokinin infusion. RESULTS: An improvement in sensitivity, specificity, efficiency and negative predictive value was obtained by second harmonic imaging compared with conventional ultrasonography. CONCLUSIONS: Second harmonic imaging, in our experience, is a reliable non-invasive tool for the diagnosis and follow-up of biliary sludge in the course of 'idiopathic' pancreatitis.

Action of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit.

The aim of this work was to compare the action of gastrointestinal (GI) hormones on the myoelectrical activity of the sphincter of Oddi. Using an experimental design previously described, we studied the electrical activity of the sphincter of Oddi and compared the percentage variation in the number of spikes before and after injection of hormones. Increasing doses of the following hormones were injected i.v. at random: CCK, OP-CCK, caerulein, bombesin, gastrin, secretin and glucagon. CCK and caerulein (as previously found), and also bombesin, OP-CCK and gastrin increased the spikes activity of the sphincter of Oddi. Secretin had no effect and glucagon decreased this activity. There was no tachyphylaxis, but a good dose-effect relationship for each hormone. Compared on a molar basis caerulein is 8 times more effective than CCK and OP-CCK which in turn are more potent than bombesin. Gastrin acts only at pharmacological doses.

Typhlitis complicating induction therapy in adult acute myeloid leukemia.

In a retrospective analysis of 161 consecutive adult patients with de novo acute myeloid leukemia undergoing induction therapy, including cytarabine, etoposide and anthracyclines, seven patients (4.3%) developed typhlitis. All presented severe neutropenia, fever, abdominal pain and tenderness within 16 days from starting chemotherapy (median 11 days; range 5-16). Three patients underwent surgery and survived, four were treated only with supportive therapy: two recovered and two died. In our experience early recognition of typhlitis and rapid recovery of the neutrophils are the most important determinants of the results of surgical and/or medical approaches. The management of typhlitis, a life-threatening condition, is controversial and depends on many factors characterizing each patient, which must be evaluated in collaboration between the surgeon and the hematologist.

Insulin-like growth factor-1 and insulin-like growth factor receptor in thyroid tissues of patients with Graves' disease.

Growth factors are frequently involved in the regulation of mitosis and differentiation of several cell types and insulin-like growth factor-1 (IGF-1) is actively involved in the thyroid stimulating hormone-mediated proliferation of thyrocytes. In view of the pivotal role of IGF-1 in thyrocyte proliferation and of the still unsettled role of this growth factor in the pathogenesis of hyperplastic thyroid lesions, we investigated the expression of IGF-1 and of its corresponding receptor, by means of immunohistochemistry, in the surgical specimens obtained from six patients with Graves' disease. Moreover, IGF-1 mRNA expression was analysed in one such case by means of Northern hybridisation. All samples showed consistent intracytoplasmic immunoreactivity for both IGF-1 and IGF-1 receptor; the vast majority of hyperplastic thyrocytes were strongly decorated by the two antibodies used in this study whereas stromal cells displayed IGF-1 immunoreactivity only. IGF-1 mRNA was markedly overexpressed in Graves' disease in comparison with normal thyroid tissues. The results of this study suggest that IGF-1 and IGF-1 receptor may be actively involved in the pathogenesis of Graves' disease; furthermore, IGF-1 and IGF-1 receptor apparently act by different mechanisms (paracrine vs. autocrine) as suggested by their differential expression in epithelial and stromal cells.

Surgical treatment of chronic pancreatitis. Report of 134 cases treated by resection or drainage.

One hundred thirty-four patients (123 men and 11 women) were operated on for chronic pancreatitis (69 pancreaticojejunostomies, 20 cytopancreaticojejunostomies, 22 left pancreatectomies, and 23 Whipple operations). Half of these patients were followed up for 5 years or more. Four patients died from cancer of the pancreas. The operative mortality rate was 4.2 percent after anastomosis, 13.5 percent after pancreatectomy, and 8.7 percent after a Whipple operation. Relief of pain was the main aim of operation. The rate of good results after pancreaticojejunostomy (85 percent) was higher than after resection (71 percent after right pancreatectomy or Whipple operation and 66.6 percent after left pancreatectomy). The mortality rate after 5 years 26 percent after anastomosis, 30 percent after Whipple operation, and 45 percent after left pancreatectomy. Alcoholic intake did not appear to influence the operative result but improved the quality of life of the patient. Postoperative complications are more common and more serious after resection than after anastomosis. If dilated, the common bile duct must be drained as well as the pancreatic duct after anastomosis. Whenever the pancreatic duct is dilated more than 8 mm it must be drained rather than resected.

An unusual complication resulting from surgical treatment of periampullary tumours.

BACKGROUND AND METHODS: The authors describe the rising of four postoperative pancreatic pseudocysts in a series of 20 patients treated for periampullary tumours by pancreaticoduodenectomy (PDT), with the closure of pancreatic stump, between 1989-1996. The operation was always performed by the pylorus-preserving technique according to Traverso-Longmire. RESULTS: In four patients (20%) 3, 4, 4, and 8 months after PDT with closure of the pancreatic stump, the authors observed the development of pseudocysts (PPC) in the pancreatic remnant. All these patients previously had a pancreatic fistula. Three symptomatic patients underwent surgical drainage of the pseudocyst in a jejunal loop (2) or in the stomach (1); in the asymptomatic patient, the clinical feature and the size of the cyst allowed for conservative treatment. In 2 cases PPC was the consequence of a pancreatic fistula evolved in acute pancreatitis of the stump. The PPC drained by cystogastrostomy appeared 4 months after the closure of the pancreatic fistula: the pancreatic stump was completely substituted by a cyst presenting a communication with the pancreatic duct. CONCLUSIONS: The authors conclude that PPC is a rare complication of the pancreatic resection that results from acute or chronic pancreatitis; sometimes pathogenesis is due to a cyst resulting from the pancreatic duct occlusion by phlogistic tissue as a consequence of the surgical suture.

Management of narrower anastomotic colonic strictures. Case report and proposal technique.

Management of narrower (<5-mm) colonic anastomotic stricture mainly is performed endoscopically by repeated balloon dilation often ineffectively. The use of metal self-expanding stents in the malignant and benign stricture of the large bowel has been suggested only recently, and is still being debated. In this report we propose a single-stage procedure that we developed to manage narrower anastomotic colonic stricture. A 60-year-old man 2 years previously had undergone surgery for perforated sigmoid diverticulitis by means of Hartmann's procedure. He was submitted to two mechanical recanalization attempts, both of which failed with dehiscence of anastomoses. He reached us with a significant stricture of the colorectal anastomoses (smaller than 5 mm in diameter) and a diversion ileostomy. After two endoscopic balloon dilations, we observed the relapse of the anastomotic stricture, so we decided to draw up another strategy. We performed a dilation with a TTS balloon, leaving a metallic self-expanding covered stent in situ for 3 months. The aim was to achieve the definitive healing of the anastomotic scar tissue at the desired diameter. We removed the stent during the ileostomy closure. At the time of this writing, 18 months of follow-up evaluation, the patient defecates without any problem

One-day vs standard thyroidectomy. A perspective study of feasibility.

BACKGROUND: The aim of this randomized controlled trial is to evaluate the feasibility of one-day thyroidectomy, comparing the results of this method vs standard thyroidectomy. METHODS: From June 2000 to June 2001, 110 patients underwent total thyroidectomy under general anesthesia for thyroid disease. The patients were randomized into 2 groups: in group A (40 patients) we used the one-day thyroidectomy; in group B (70 patients) we employed standard thyroidectomy. In both groups postoperative mobilization was immediate and the mean postoperative hospitalization stay was 21 hours (range: 18-24) in group A and 60 hours (range: 21-120) in group B. The mean follow-up was 10 months (range: 6-18 months). RESULTS: The patients of group A showed hypoparathyroidism with temporary hypocalcaemia in 3 cases (7.5%) vs 5 (7.1%) of group B; this finding was not statistically significant. No cases of definitive hypoparathyroidism, nor lesions of RLN, of the external branches of the superior laryngeal nerve, nor postoperative hemorrhage were observed in either group. CONCLUSIONS: The one-day thyroidectomy was found to be a safe, feasible and cost effective procedure, it is convenient for both the patient and the surgeon, and offers the same immediate and long-term results as the standard thyroidectomy in selected patients.

[The Boario project. A study of the prevalence of lithiasis in a spa population]. / Progetto boario. Studio della frequenza della malattia litiasica in una popolazione termale.

In order to better evaluate some epidemiological findings observed during previous studies on large samples of free living populations we carried out a case-control study on a randomly selected group of subjects in a health spa, Boario Terme. Seven-hundred and thirty subjects, aged 40-69 years, participated in the study. The study protocol included an ultrasonographic examination of the upper abdomen, a physical examination, a questionnaire, and a blood sample. Prevalence of gallstone disease was two times higher in females (37.2%) than in males (19.7%) (RRMH = 1.88). Fifty out of the 80 gallstone subjects were not aware of the disease prior the study (62.5%), and 60 did not experience any specific biliary symptom (colic) in the 5 years prior the study. The so-called "nonspecific symptoms" were not found related to gallstone disease. Gallstone disease was positively related to number of pregnancies, obesity, and economical status. In conclusion the present study confirmed some results observed during previous epidemiological studies. In regards to symptoms present data suggest that biliary colic is the only specific symptom for gallstone disease. In addition, the high number of asymptomatic gallstones observed in this study suggests the need of more investigations on high-risk populations in order to make earlier diagnosis and eventually to prevent the disease.

Ultrasound duplex as a sole exam for surgical purposes in lower limb arterial obstructive disease.

BACKGROUND: The aim of the research is to value the efficacy of ultrasound duplex as a sole preoperative exam in peripheral Arterial Obstructive Disease (PAOD). Angiography is undoubtedly known as the gold standard, though its risks and complications. In the last decades duplex scanning and its variant, has proven to be an irreplaceable tool in the diagnosis of these disease. METHODS: We evaluated five previous studies that compare angiography to duplex scanning. RESULTS: Out of 273 cases, 207 (73.8%) had a good correspondence between the two methods; besides if we consider each arterial tract duplex reliability is better in distal diseases (159 cases out of 200, 79.5%) than in proximal (48 out of 73.65%) contrasting with an other meta-analytic evaluation made by Koelemay et al. Moreover we wanted to verify our personal experience, by the intention to treat method, if the surgical operation selected for our patients would have been the same based only on pre-operative echo-duplex scanning. After the analysis of about 20 files the research was interrupted because there was a perfect correspondence between the two exam only in three cases, all of them re-operation for graft branches obstruction. The lacks of duplex has been: 1) non identification of important lesions on the aorto-iliac tract; 2) insufficient location of distal disease. CONCLUSIONS: The angiography results the fundamental choice in the treatment of PAOD particularly in the distal tracts. Debatable is the role of echography in aorto-iliac portion, where a number of lesions may be effectively treated by endovascular procedures.

Surgery of abdominal aorta in octogenarians. Can indications be extended?

BACKGROUND: This paper describes the authors' experience with the management of the abdominal aorta in patients aged over 80 years. METHODS: Ten urgent procedures were performed on patients older than 80 years during a 2 year period. In 4 cases surgery was performed because of a ruptured aneurysm of the subrenal abdominal aorta, in 2 cases for active symptomatic aneurysms, in 3 cases for severe lower limb ischemia (occlusion of the iliac and femoral arteries) and in 1 case for a secondary aortoenteric fistula. RESULTS: The operative mortality rate was 20% (2 cases with a ruptured aneurysm). Five patients are still alive in good health conditions (one of them had been operated twice for two different diseases). Even if our findings refer to a small number of patients, although similar series on emergency operations found in the literature are not substantially larger, the results do not advise against operative treatment of the abdominal aorta in cases requiring a direct approach, even in patients over 80 years of age. CONCLUSIONS: If this treatment strategy is obviously adopted in emergency conditions, as with the patients we are reporting on, since the alternative to operation is usually death, it should also be carefully considered in elective circumstances, where alternative treatments such as endovascular stents did not to date obtain better results. In the elective scenario all the necessary biological and physical parameters as well as the patient's age should be taken into proper account in deciding whether to operate. This is specially true now that the average life spans of an individual is longer so that patients, who may incur serious problems if left untreated, may be offered a better quality of life.

[Criteria of evaluation of hemorrhagic portal hypertension and surgical indications]. / Criteri di valutazione nell'iperteso portale emorragico e indicazioni chirurgiche

Massive, active bleeding of the oesophageal varices in cirrhotics requires immediate, comprehensive and continuing appraisal of determining risk parameters (liver function and morphology, hyperdynamic syndrome, renal function, dynamic angiography of the splanchnic circulation). When survival is linked with stopping the haemorrhage, indications must not be looked at restrictively and operation has to be fast. Minor surgical measures aimed at temporary control of the haemorrhage are not satisfactory. Side-to-side portacaval anastomosis is effective in terms of reducing portal pressure and controlling the haemorrhage. Mesenterico-caval shunt with H-dacron graft interposition is sufficient dynamically and has less effect on porto-hepatic flow. Long-term results with this technique requires further study.

[Early colorectal reoperation: risk factors]. / Reinterventi precoci in chirurgia colorettale: fattori di rischio.

The aim of the study was to analyse the risk factors in colorectal reoperation. Over the period from January 1987 to December 1999, 371 patients (191 male and 180 female, aged from 16 to 88 years) underwent colorectal surgery. Eighteen reoperations (12 male, 6 female, aged from 20 to 74 years; median age: 52.6 years) were performed. These included reoperations performed within 30 days of the first operation (or patient admission). The overall incidence of reoperation after colorectal surgery was 4.8% (18/371). In 14 of 18 patients (77%) anastomotic dehiscence was the indication for reoperation. In our experience, the mortality rate was 16.6% (3/18), in agreement with other reports in the literature. Analysis of risk factors in colorectal reoperation poses several methodological problems because we have no randomized multicentre studies that analyse risk factors in colorectal reoperation and the related surgical mortality.

[Preliminary experience with the surgical treatment of inguinal hernias with the Shouldice procedure]. / Considerazioni sulla iniziale esperienza nel trattamento chirurgico delle ernie inguinali secondo la tecnica di Shouldice.

The authors report their recent experience on the surgical treatment of inguinal hernias according to Shouldice Canadian repair, used for the undiscussed advantages. The least pre-operational preparation, the early mobilization of the patient, the reduction of the hospitalization and the almost total absence of relapses, support the application of this technique of which we auspicate a wider use.

[Traumatic retroperitoneal lesions]. / Lesioni traumatiche retroperitoneali.

The presence of lesions on the retroperitoneum generally worsens the prognosis in traumatic pathology; it implies more attention and skills from both the medical and surgical aspect. All type of trauma, blunt or open, may involve retroperitoneal structures and organs; specifically there may be lesions on the great vessels, pancreas, duodenum, oesophagus and genitourinary apparatus. Mortality is high, compared to abdominal traumatic lesions confined within the peritoneal sac. Treatment of single or associated lesions requires a multidisciplinary approach, as the surgical repair implies a specific knowledge and experience on different organs, whose habitual pathology lies on the hands of more surgical specialists. Lesions of great vessels are immediately life-threatening; moreover the choice to "open" a patient for a retroperitoneal hematoma has to be taken upon a careful estimation. It could be better in more than a situation leave such hematoma in its place, specially in the iliac region, waiting for the spontaneous resolution of the hemorrhagic source and of the hematoma itself. The involvement of oesophagus, duodenum or pancreas determines instead a poorer prognosis at a distance. In conclusion retroperitoneal traumatic lesions are among the most challenging and serious emergencies, and necessitate a maximum of attention and expertise by the surgical team involved. Only with a careful judgement about the tactics and the procedures to carry on it is possible to obtain valid results, which often means to safe the patients life.

[Right abdominal colonic masses. Recent diagnostic and therapeutic advances: personal experience]. / Masse addominali destre di appartenenza colica. Recenti acquisizioni diagnostiche e terapeutiche: esperienza personale.

The authors, referring to their experience, make a review of colic pathological features presenting as right abdominal mass. Despite of modern diagnostic means--specially radiological investigations: ultrasonographic and CT scanning--accurate clinical examination still plays a role in the initial assessment and to address diagnostic procedures. Diagnosis may be difficult as the right colon is hardly accessible even to present investigative means. US scanning has proved to be useful, in the surgeon's hands, for timely detection of the lesion and in monitoring its evolution. Many diseases must be considered in the diagnosis of a right colon mass and a few rare too: Meckel diverticolitis, carcinoid, vermiform appendix pseudomyxoma, amebic granuloma, Kaposi's sarcoma. Treatment is still an intriguing question, depending on many factors: site, kind and variety of the diseases showing as right abdomen mass, difficulty in early diagnosis, risk of misdiagnosing, shortage of series reported in literature and the absence of multicenter studies.

[Urgent ulcerative colitis: our experience]. / Rettocolite ulcerosa in urgenza ed emergenza: nostra esperienza.

The authors refer their experience in Urgent Ulcerative Colitis. They define the various clinical maniferstations and then specify the necessary elements for a corrent nosological arrangement. About diagnosis, their confirm the inconvenience of clinical examination like as colonscopy or an opaque clysma, giving their choice to other parameters, like as clinical, hematic (PCR), microscopic and cultural of the faeces, radiological (direct abdomen radiography; abdomino-pelvic echography; abdomino-pelvic TC, better if spiral), endoscopic (rectoscopy with minimal insufflation). They explain their guideline about medical therapy, the strategy adopted in relation to its duration, the protocol of evaluation during the administration period and the predictive sighs of its possible failure. After having precised the surgical indications, they stop a little about the timing of a surgical interventation, underlining its primary importance. In the range of a surgical strategy. They give their choice to the total colectomy with associated ioleostomy for its less incidence of complications and mortality versus proctocolectomy, reserving this last one to that cases with irreprensible rectal hemorragy, with preservation of the anal canal for a possible delayed ileo-anal anastomosis. They also think, at last, that after an Urgent Total Colectomy, the immediate ileo-rectum anastomosis could have an high risk of dehiscence of the anastomosis itself and so it must be reserved only to that selected cases which offer local and general guarantees of solidity of the anastomosis and it must be preferably done joinly whit a loop ileostomy at the bottom of the anastomosis itself.