Systemic involvement in adult-onset leukoencephalopathy with intracranial calcifications and cysts (Labrune syndrome) with a novel mutation of the SNORD118 gene.

BACKGROUND AND PURPOSE: Although Labrune syndrome is a well-known disorder characterized by a typical neuroradiological triad, namely leukoencephalopathy, intracranial calcifications and cysts, there are no reports of systemic involvement in this disorder. This paper attempts to describe a peculiar clinical manifestation related to a novel mutation in the SNORD118 gene. METHODS: Clinical examination, brain and total-body imaging, and neurophysiological and ophthalmological investigations were performed. Amplification of the SNORD118 gene and Sanger sequencing were integrated to investigate potential causative mutations. RESULTS: A 69-year-old woman, with a long history of episodes of vertigo and gait imbalance, was referred to our hospital for progressive cognitive and motor deterioration. Computed tomography and magnetic resonance imaging disclosed diffuse bilateral leukoencephalopathy in periventricular and deep white matter, widespread calcifications and numerous cysts in the brain, liver, pancreas and kidneys. The genetic analysis revealed two biallelic variants in the SNORD118 gene, one of which is novel (n.60G>C). CONCLUSIONS: This is the first report of adult-onset Labrune syndrome with an unusual systemic involvement presenting a novel mutation in the SNORD118 gene.

High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures. MATERIALS AND METHODS: A specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded. RESULTS: All patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1-3 days after treatment. CONCLUSIONS: According to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial.

BACKGROUND: Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS: Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patient's death or ending of the study. RESULTS: Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS: Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

Long-term endoscopic and clinical follow-up of untreated type 1 gastric neuroendocrine tumours.

BACKGROUND AND AIMS: Type 1 gastric neuroendocrine tumour surveillance and treatment are a matter of debate. Endoscopic, or surgical, resection and chronic somatostatin analog therapy have been proposed. Based on the favourable behaviour of this neoplasm, we performed an endoscopic and clinical follow-up in 11 patients affected by type 1 gastric neuroendocrine tumours, avoiding any specific treatment. METHODS: Between 1994 and 2006, we prospectively recorded the data of 11 untreated patients with type 1 gastric neuroendocrine tumours who underwent an endoscopic and clinical follow-up. All the patients were also evaluated by means of an abdominal computed tomography scan, somatostatin receptor scintigraphy and blood tests. RESULTS: During the follow-up (median 54 months, range 9-136), the endoscopic picture of 4 (36%) out of 11 patients changed in terms of increased number of lesions. In none of the cases were detected any lesions that exceeded 10mm in diameter, and none of the patients demonstrated any evidence of local or distant metastases. CONCLUSIONS: Our data confirm the literature data of the indolent behaviour of type 1 gastric neuroendocrine tumours and suggest that a careful endoscopic follow-up, without any treatment, might represent a reasonable and safe option in selected patients.

Tips and tricks for a safe and effective image-guided percutaneous renal tumour ablation.

Image-guide thermal ablations are nowadays increasingly used to provide a minimally invasive treatment to patients with renal tumours, with reported good clinical results and low complications rate. Different ablative techniques can be applied, each with some advantages and disadvantages according to the clinical situation. Moreover, percutaneous ablation of renal tumours might be complex in cases where there is limited access for image guidance or a close proximity to critical structures, which can be unintentionally injured during treatment. In the present paper we offer an overview of the most commonly used ablative techniques and of the most important manoeuvres that can be applied to enhance the safety and effectiveness of percutaneous image-guided renal ablation. Emphasis is given to the different technical aspects of cryoablation, radiofrequency ablation, and microwave ablation, on the ideal operating room setting, optimal image guidance, application of fusion imaging and virtual navigation, and contrast enhanced ultrasound in the guidance and monitoring of the procedure. Moreover, a series of protective manoeuvre that can be used to avoid damage to surrounding sensitive structures is presented. A selection of cases of image-guided thermal ablation of renal tumours in which the discussed technique were used is presented and illustrated. TEACHING POINTS: • Cryoablation, radiofrequency and microwave ablation have different advantages and disadvantages. • US, CT, fusion imaging, and CEUS increase an effective image-guidance. • Different patient positioning and external compression may increase procedure feasibility. • Hydrodissection and gas insufflation are useful to displace surrounding critical structures. • Cold pyeloperfusion can reduce the thermal damage to the collecting system.

Treatments for colorectal liver metastases: A new focus on a familiar concept.

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised.

Management of retrosternal goiters: experience of a surgical unit.

The aim of this study was to retrospectively analyze 5 years' experience of cervico-mediastinal goiters (CMG) management. Twenty-five patients with cervico-mediastinal goiters underwent surgery between January 1998 and December 2002. The group consisted of 16 females and 9 males (mean age, 48.2 years; range, 42-74 years). A total thyroidectomy under general anesthesia was always performed. A no. 7 Fogarty catheter with a 5-ml balloon was employed in the seven last cases to lift the retrosternal portion of the goiter into the neck. The mean postoperative stay was 3 days (range, 1-7 days), and the mean follow-up time was 29 months (range, 1-58 months). There were no postoperative deaths; overall morbidity rate was 28.0%. One patient with a severe life-threatening hematoma required surgical re-exploration. Surgery for CMGs shows a low morbidity rate; total thyroidectomy is the treatment of choice to prevent recurrences or re-surgery for malignancy.

Hepatic intra-arterial chemotherapy using a percutaneous catheter in pretreated patients with metastatic colorectal carcinoma.

BACKGROUND: Hepatic intra-arterial chemotherapy (HIAC) leads to a higher response rate than systemic administration in untreated patients with liver metastases from colorectal cancer (CRC). The aim of this study was to evaluate the activity and safety of giving HIAC through a percutaneous catheter in pre-treated patients. PATIENTS AND METHODS: Forty-five CRC patients with liver-only or liver-dominant metastases, resistant or refractory to previous systemic therapy, were treated using a temporary trans-subclavian catheter. A 3-day chemotherapy regimen of daily 5-fluorouracil (5-FU) 1000 mg/m2/day + heparin 5000 IU/day given as a 24-hour continuous infusion, and twice daily bolus injections of cisplatin (CDDP) 10 mg/m2 and mitomycin C (MMC) 2 mg/m2, was administered every six weeks. RESULTS: One hundred and seventeen courses were administered to 45 patients (a median of three per patient: range 1-5). Of the 44 patients evaluable for response, 16 (35%) had a partial response, 15 (33%) stable disease and 12 (26%) progressive disease. Eleven of the 16 responding patients had been refractory to a previous 5-FU-based systemic therapy. The most relevant grade 3-4 toxicities included neutropenia (22%) and thrombocytopenia (15%). Gastro-duodenal ulcers occurred in nine patients. Catheter displacement was recorded during 22 out of 117 (18%) courses. CONCLUSION: HIAC with 5-FU, CDDP and MMC given through a temporary percutaneous catheter is safe and active in pretreated patients with metastatic CRC. Iatrogenic gastroduodenal ulcers are a serious but manageable complication.

The uncertain primary diagnosis of inflammatory bowel diseases.

BACKGROUND: The purpose of this study is to re-evaluate our series of patients affected by a colonic non-neoplastic disease, in order to measure the percentage in whom we were unable to make a correct diagnosis after the first clinical and histological approach and to single-out the reasons for our inability to reach the correct diagnosis. METHODS: During the period 1985-1999 we observed 1228 patients affected by chronic inflammatory colonic diseases. RESULTS: In 859 patients (69.9%) an ulcerative colitis was diagnosed for the first time, and 248 patients (20.1%) were affected by Crohn's colitis. One hundred and twenty-one patients (9.8%) were defined as being affected by an undetermined colitis. Forty-three patients of these had a definite diagnosis, afterwards: 27 patients were affected by ulcerative colitis and 16 by Crohn's colitis. Differential diagnosis between inflammatory large bowel diseases (ILBD) and other forms of colitis was set out as follows: 62 cases out of 1228 were consequent on a bacterial infection or parasitosis; in 28 patients a colitis pseudomembranosus was diagnosed. Eighteen cases of ischemic colitis are reported and 14 patients were affected by NSAID-related colitis. In another 6 patients we diagnosed a postradiation colitis. In 22 cases mimicking a Crohn's colitis we ascertained 9 patients affected by intestinal lymphoma, 11 mycobacterium tuberculosis related intestinal infections and 2 cytomegalovirus related colitis. CONCLUSIONS: Despite progress in scientific acquisitions and in diagnostic methods, correct initial diagnosis of ILBD is still difficult, even though it will be defined with time.

Definitive palliation for neoplastic colonic obstruction using enteral stents: personal case-series with literature review.

Acute colonic obstruction due to malignancies is an emergency that requires surgical treatment. Elderly patients or inoperable tumors require intestinal decompression that is a simple colostomy in almost all cases. This "manoeuvre" leads the patient to a percentage of mortality/morbidity and to a bad quality of life due to acceptance of stoma. The introduction of enteral metal stent inserted endoscopically has, in our opinion, provided a new way to obtaining the definitive palliation of inoperable colo-rectal cancer with a simple method. We reported our case-series and we analyzed the current literature and costs of treatments.

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.

Risk factors of morbidity in thyroid surgery: analysis of the last 5 years of experience in a general surgery unit.

The aim of this retrospective study is to analyze the risk factors of morbidity in thyroid surgery. From January 1997 to December 2001, 343 patients (69 males and 280 females, mean age 46.1) who underwent surgery under general anesthesia for thyroid disease were analyzed. In 22 (6.4%) cases the operation was a second thyroidectomy. The mean post-operative stay was 2 days (range: 1-7) and the mean follow-up was 21 months (range: 1-60 months). Statistical analysis of our data was performed by chi-square test and confirmed by Fisher exact test. The statistical analysis showed the significance of malignancy and re-surgery as risk factors of hypoparathyroidism and recurrent laryngeal nerve palsy. Sex, age, and type of operation had no influence on the medical records. The completion of thyroidectomy and histological malignancy increase the morbidity of thyroid surgery.

Rectal perforations. Personal experience and literature review.

BACKGROUND: Rectal perforation presents high morbidity and mortality and its treatment is still not standardized, it is still rather based on the surgeon's personal experience. This retrospective trial, with a literature review, aims to define these types of lesions, and tries to identify the diagnostic and therapeutic options able to reduce related morbidity and mortality. METHODS: On 1175 operations conducted for colo-rectal emergency, over a ten-year period at our institution, fourteen consecutive patients (1.2%) were seen and treated for rectal perforation. In 43% of cases the treatment consisted in Hartmann's procedure, in the 28.5% ones in rectal wound repair with diverting colostomy and in 28.5% left in diverting colostomy alone. RESULTS: There were no postoperative complications in 86% of patients, and no deaths from sepsis. In 28.5% of cases intestinal continuity was restored at our institution. CONCLUSIONS: Our results demonstrate that a standardized protocol which is based on patients' conditions, type and degree of rectal injury and of peritonitis, must be followed in order to determine the type of surgical option and consequently to reduce the morbidity and mortality related to rectal perforation.

Trabucco versus Rutkow versus Lichtenstein techniques in the treatment of groin hernia. A controlled randomized clinical trial.

BACKGROUND: The aim of this prospective study is to compare the results of the 3 most common tension-free techniques usually performed (Trabucco vs Rutkow vs Lichtenstein). METHODS: From January 1993 to December 1995 we selected 150 patients to undergo elective surgery for primary monolateral inguinal hernia. The patients were randomized into 3 groups: in group A (53 patients) we used the original plug and patch technique proposed by Rutkow and Robbins; in group B (47 patients) we introduced a modification to the technique originally described by Trabucco, anchoring the plug to the internal ring, fixing the patch on the pubic tubercle and on the tails of the mesh; in group C (50 patients) the Lichtenstein technique was employed. The study was performed using a randomized single blind controlled trial (RCT). The statistical analysis of our data was performed by c2 test and confirmed by the Fisher exact test. The mean follow-up was 73 months (range:58-94). RESULTS: We had no statistically significant differences in the results of the 3 groups. Otherwise the patients of group C showed a significantly higher incidence of suprapubic or more rare inguino-scrotal haematoma (p<0.0033 C vs B; p <0.0038 C vs A). The mean recovery time was between 12 and 14 days in the 3 groups, with no significant statistical differences. CONCLUSIONS: The only difference observed is a higher incidence of postoperative haematoma in group C.

[The indications and surgical treatment in the complications of colonic diverticular disease]. / Indicazioni e trattamento chirurgico nelle complicanze della malattia diverticolare del colon.

In this work the authors describe the different stages of diverticulosis and analyze the pathogenetic principal factors. During the period from 1979 to 1998 they observed 420 patients affected by diverticular disease (224 M; 196 F), 42 (10%) of them were operated on for complications. Fifteen patients operated on in elective time underwent a one stage procedure of resection and anastomosis with derivative colostomy; 27 patients were operated on in emergency: 6 patients had one stage procedure of resection and anastomosis with derivative colostomy, 16 patients Hartmann's procedure, 3 patients Mikulicz's procedure and 2 patients colostomy and peritoneal drainage. Two patients died from septic shock. There was absence of postoperative complications for the patients operated on in elective time, while 8 cases (29.6%) showed peritoneal sepsis and 4 cases (14.8%) infection of wound in the patients operated on in emergency. The Authors describe the different surgical options in the treatment of colonic complicated diverticular disease and conclude that the surgical treatment is not definite. A tendency is to make a one-stage procedure of resection and anastomosis and to reduce the Hartmann's procedure or the simple colostomy with drainage of abdominal cavity.

[Cell-mediated immunity and delayed hypersensitivity study in splenectomy patients: a comparative evaluation between IFN-gamma and skin tests]. / Studio dell'immunità cellulo-mediata e dell'ipersensibilità ritardata negli splenectomizzati: valutazione comparativa fra IFN gamma e skin tests.

The authors of this paper attempt to indicate a feasible, easy-to-use and inexpensive instrument for daily assessing and monitoring of splenectomized subjects to see if they are immunocompromised. Skin tests which are considered easy and inexpensive, may be useful for immunological investigation if their effectiveness is considered equal to that of more difficult and expensive methods. They have also assessed the effectiveness of ST in the study of specific cell-mediated immunity in general and also in cases of delayed hypersensibility, comparatively to serum IFN gamma dosage. The latter is produced by Th1 lymphocytes and Natural Killer cells and is considered a reasonable indicator of cell-mediated immunity and Th1-related delayed hypersensibility. The results of this study confirm that ST is effective in 100% of all splenectomized patients compared to positivity of 60% for the compromise of the immunocompetent system revealed by serum IFN gamma dosage in the same sample of patients. In addition, the fundamental role of other cytokines was confirmed. These include IL-2 which is produced by Th1 lymphocytes and whose lack of results in splenectomized patients are immunocompromised. This is revealed not only by IFN gamma dosage but also by ST.

[Appendiceal carcinoid. Clinical observations and therapeutic considerations]. / Il carcinoide dell'appendice. Osservazioni cliniche e considerazione terapeutiche.

The Authors report 3 cases of carcinoid of the appendix discussing the difficult preoperative diagnosis and the different therapeutical options. Between May 1998 and August 1999 36 appendicectomies were performed, in 18 males and 18 females (age 14-89 years; m. a.: 51.5 years). In 3 cases histological response was positive for carcinoid of the appendix. No postoperative mortality or morbility was reported. In one case, the malignancy of histological response made a second operation of typhlectomy necessary, without postoperative complications. The Authors analyze the biological peculiarities and the prognostic factors of appendiceal carcinoid tumors, as size of the tumor and the lymphatic or vascular infiltration of the mesoappendix (and the relative more aggressive surgical treatments) and recommend an appropriate postoperative follow-up since synchronous or metachronous bowel carcinomas are likely to occur.

[Th1-Th2 cytokine correlates (INF-gamma and IL-4) in splenectomized patients]. / Studio delle citochine Th1-Th2 correlate (IFN gamma e IL-4) negli splenectomizzati.

This paper attempts to explain if immunodepression in patients who had undergone a splenectomy may be due to altered balance between Th1-Th2 lymphocyte subpopulations, as shown in several studies on phagocyte and lymphocyte cells. This was achieved by dosing serum levels of IFNg, produced by Th1 lymphocytes and IL-4, produced by Th2 lymphocytes. Final analysis showed immunodepression in splenectomized patients but also emphasized that in 70% of all cases, there is functional damage of T-lymphocytes that continues for several years after the surgery involving both cellular and humoral immunity. Immunoglobulin dosage allows the increase of IgE to be seen in 50% of the splenectomized patients studied, all with allergic symptoms that appeared after the operation. The production of IgE is stimulated by Th2 lymphocytes. This leaves one to believe that splenectomy may favour the persistence of allergens in the blood, the appearance of allergic symptoms and the increase of IgE serum levels in patients with normal Th2 functioning and consequently, with normal or increased IL-4 serum levels.

[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.