Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Is elastography actually useful in the presurgical selection of thyroid nodules with indeterminate cytology?

BACKGROUND: Although fine-needle aspiration cytology remains the mainstay of the preoperative workup of thyroid nodules, those with follicular proliferation still represent a diagnostic challenge. Real-time elastography (RTE) estimates the stiffness/elasticity of lesions and is regarded as a promising technique for the presurgical selection of thyroid nodules (including those with indeterminate cytology). AIM: Our aim was to verify the potential role of RTE in the presurgical diagnosis of cancer in a large cohort of consecutive patients with follicular thyroid nodules. PATIENTS AND METHODS: One hundred two patients were submitted to conventional ultrasonography and RTE evaluation before being operated on for thyroid nodule with indeterminate cytology (54% single nodules). Tissue stiffness on RTE was scored from 1 (greatest elasticity) to 4 (no elasticity). RESULTS: At conventional ultrasonography examination, the nodules (median diameter 2.2 cm) were solid (cystic areas < 10%); microcalcifications were detected in 56% of them and a hypoechoic pattern in 64%. Elasticity was high in eight cases only (score 1-2) although low in 94 (score 3-4). Cancer was diagnosed in 36 nodules (35%), being associated with microcalcifications (P < 0.0001) and inversely related to nodule diameter (P < 0.01). Malignancy was detected in 50% of the nodules with RTE score 1-2 and in 34% of those with score 3-4. Therefore, either the positive (34%) or the negative predictive value (50%) was clinically negligible. CONCLUSIONS: The current study does not confirm the recently reported usefulness of RTE in presurgical selection of nodules with indeterminate cytology and suggest the need for quantitative analytical assessment of nodule stiffness to improve RTE efficacy.

Critical US visibility with tissue harmonic imaging of subcutaneous nodules().

INTRODUCTION: Assessment of US ability to identify subcutaneous nodular lesions using conventional B mode imaging (CBMI) and tissue second harmonic imaging (THI). MATERIALS AND METHODS: Three different types of equipment were used (Philips Envisor HDC, Philips HD 11 XE and GE Logic E) with 12-13 MHz probes and THI probes with variable frequency. One experienced operator studied 31 patients (24 women, 7 men, mean age 49 ± 15) with 52 subcutaneous nodular lesions of which 43 were palpable and 9 were nonpalpable. Statistical analysis was carried out using chi-square test. RESULTS: 19/52 subcutaneous nodular lesions were hyperechoic, 10/52 were isoechoic and 23/52 were hypoechoic. Of the hyperechoic nodules, 8/19 (42%) (p < 0.005) were not detected using THI, as they "disappeared" when THI was activated. Of the isoechoic nodules only 1/10 was not detected using THI, and of the hypoechoic nodules only 2/23 were not detected. Of the nodular lesions detected using CBMI and also using THI (41/52), 16/41 were shown more clearly using THI than using BMCI. No nodule was detected with the exclusive use of THI. CONCLUSIONS: The statistical significance of the "disappearing" lesions (p < 0.005), mainly hyperechoic (42%), at the activation of THI must lead to a reconsideration of routine activation of THI during the entire US examination in the evaluation of subcutaneous lesions in order to avoid the risk of missing important lesions. The present results suggest that both BMCI and THI should be used in the study of subcutaneous lesions.

[Primary allergy prevention: partially or extensively hydrolyzed infant formulas?]. / Prevenzione dietetica primaria dell'allergia: idrolisati parziali o estensivi?

The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. In infants from ''high-risk'' families (i.e. those with one or two parents and/or a sibling with food allergy, eczema, asthma or allergic rhinitis) food allergen avoidance has been advocated as means of preventing the development of atopic disease. The aim of this review was to evaluate the allergy preventive potential of partially or extensively hydrolyzed formulas. When breast-feeding is not possible or supplemental feeding is needed, infants from atopic families should be given a hydrolyzed infant formula for the first 6 month of life. High-risk infants without a history of eczema in a primary relative will receive the protective effect from the less expensive partial hydrolyzed formula (p-HF); whereas those infants who have first-degree relatives with eczema should receive the extensively hydrolyzed formula (e-HF).

Ultrasound findings guided a successful hemicolectomy in a leukemic patient with neutropenic enterocolitis.

INTRODUCTION: Neutropenic enterocolitis (NEC) can be a life-threatening complication of chemotherapy in leukemic patients. Early diagnosis and treatment is therefore crucial. METHODS: A 38-year-old woman with acute lymphoblastic leukemia and chemotherapy-induced neutropenia suddenly developed symptoms suspicious of NEC. Transabdominal ultrasound showed features consistent with NEC, later confirmed by computed tomography (CT) scan. RESULTS: The patient was scanned using portable ultrasound (US) equipment (Esaote My Lab 25). US findings showed involvement of the cecum, appendix, ascending colon and proximal middle transverse colon, with features resembling gas containing fissures within the colon wall itself. The risk of colon rupture was confirmed by CT scan. The patient underwent successful hemicolectomy after intravenous treatment with broad spectrum antibiotics, granulocyte-colony stimulating factor (G-CSF), platelets and fresh frozen plasma transfusion. DISCUSSION: A prompt bedside US examination upon development of symptoms allowed an early diagnosis of NEC and identified features consistent with imminent colon wall rupture, shifting the management of this life-threatening complication from medical to surgical. Multidisciplinary intervention was crucial for a successful hemicolectomy in a severely affected neutropenic patient.

[Phytoterapy: a glimmer of hope in the prevention of recurrent respiratory tract infections in children]. / Fitoterapia: un barlume di speranza per la prevenzione delle infezioni respiratorie ricorrenti nel bambino.

Evidence on the efficacy of standardised phytoterapic extracts for the prevention of recurrent respiratory tract infections (RRTIs) in children is reviewed. Echinacea extracts are widely used in European countries and in the United States as immune-stimulating agents. However, further prospective, appropriately powered clinical studies are required to confirm their benefits in reducing duration and severity of RRTIs.

Laparoscopic treatment of pancreatic insulinoma.

Laparoscopy and laparoscopic ultrasonography (LUS) have been proposed for the diagnosis and treatment of pancreatic insulinoma. We present for cases of pancreatic insulinoma approached by laparoscopy guided by LUS. In three cases, insulinomas were in the pancreatic body and in one case in the pancreatic head. All lesions were detected preoperatively by abdominal US and confirmed by computed tomography. Laparoscopy was performed under general anesthesia. LUS was performed using a 10-mm flexible probe. In two cases the adenoma was enucleated using scissors and electrocoagulation, major vessels were controlled using clips, and enucleation was completed using a 30-mm endo-GIA. In one case a laparoscopic distal pancreatectomy with spleen preservation was performed. In one case the adenoma was deep in the pancreatic head; minilaparotomy was performed and the adenoma enucleated. Patients were discharged in good health 5-7 days after surgery. The postoperative course was complicated in one case of enucleation by peripancreatic fluid collection that was treated percutaneously. Our experience confirms that accurate localization followed by excision of tumors via the laparoscopic approach constitute a significant advance in the management of insulinoma.

TIMTEM project: our experience in a remote area.

We report our experience, begun in 1998 on a small island in the Dodecanese area of Greece, which has been called TIMTEM. The aim of this project was to improve care for people living on islands, creating a model exportable to other rural areas. The operative setting of the TIMTEM project is the island of Tilos (Greece); local authorities take part in it under the guidance of the only physician available on the island. The University of Pisa-Italy (Department of Surgery, Post-graduate School of Emergency Surgery) manages the scientific and organizational part of the project. Tilos is a rocky Mediterranean island with a surface of 64 km(2) and a population of about 500 inhabitants (with a peak of 2,000 tourists in July and August). A physician and a nurse are responsible for the only medical care on the island, and they also dispense drugs. The project was implemented on three phases. During the first phase, a campaign was held to encourage the population to cooperate with clinical data collection; a temporary telemedicine station was established, and a complete screening of the population was performed. The second phase was focused on the application of telesonography. During the third phase, a telematic and/or direct participation for reference hospital physicians (Regional Medical Society-Dodecanese) and for Greek physicians was planned. As well, a fully equipped central telemedicine station in the reference hospital was established under the local jurisdiction. The results of the third phase are still incomplete; the data presented here are preliminary. But all indicators show that the project is exportable to remote areas elsewhere.

Percutaneous management of multiple bilateral liver abscesses complicating Crohn disease.

Liver abscess is a rare complication of Crohn disease. A case of multiple, bilateral, pyogenic liver abscesses appearing as a recurrent manifestation of Crohn disease in a 34-year-old man is reported. Conservative management with antibiotics, double-catheter drainage, and multiple aspirations was successful. The liver abscesses disappeared with no recurrence during a 5-year follow-up period.

Laparoscopic radiofrequency thermal ablation of hepatocarcinoma: preliminary experience.

The objective was to evaluate the feasibility, safety, and effectiveness of radiofrequency thermal ablation (RFT), performed during laparoscopy with a cooled-tip electrode needle, in the treatment of neoplastic hepatic focal lesions. Seven patients with hepatocarcinoma (10 hepatic lesions) were treated during laparoscopy with RFT using a 100-watt RF generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 3-cm exposed tip. The mean exposure time was 12 minutes for each needle insertion. Spiral computed tomography scanning detected complete tumor necrosis in nine lesions; in one lesion, peripheral neoplastic tissue was detected, and percutaneous RFT was performed. Two patients during follow-up developed two new neoplastic lesions, treated with percutaneous ethanol injection. No recurrences of the treated lesions were seen after 6 months of follow up. Intraoperative RFT with a cooled-tip electrode needle is a safe and effective local treatment of hepatic focal lesions during laparoscopic surgery. Possible indications are large hepatocarcinoma (>5 cm), superficial lesions, multiple lesions, or tumor located near vascular or biliary structures.

Telemedicine on a small island.

Information on the health status of the population of a small Greek island was collected. The information consisted of personal data, clinical history, physical examination, blood pressure evaluation, electrocardiography, and ultrasound scans of neck, breast and abdomen. Ninety-six per cent of the entire island population (280 inhabitants) participated in the study. Two per cent were at risk of serious complications of pathological disease and were immediately referred to a regional hospital for adequate care while 25% had minor pathological problems. Our experience suggests that health-care workers on small islands should be trained in the use of technology as a means of communication with mainland hospitals.

[Echography in the surgical emergency]. / L'ecografia nell'urgenza chirurgica.

Abdominal sonography represents the diagnostic method of choice in case of acute abdomen. On the bases of their experience on more than 1200 consecutive examinations performed in case of acute abdomen the author evaluate the fields of application of sonography in acute patients. A decisional algorithm in trauma patients based on sonographic results is presented. The actual indications of sonography abdominal non traumatic pathology are presented: paying particular attention to acute gastro-intestinal diseases. The therapeutic role of interventional sonography in the acute abdomen is also discussed.

Treatment of hyperfunctioning thyroid nodules with percutaneous ethanol injection: Eight years' experience.

The aim of our study was to define the long-term efficacy and safety of percutaneous ethanol injection (PEI) for the treatment of autonomous thyroid nodule (ATN), and to optimise the clinical usefulness of such a therapy. We treated 132 patients with ATN (30 M and 102 F, aged 47.5+/-12.9 years; mean+/-SD), in case other established treatments were refused or contraindicated. Eighty-five patients were affected by toxic adenoma and 47 suffered from pre-toxic nodules. Ethanol was administered weekly under sonographic control, in 7 sessions (range 2-16). During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. Three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra nodular tissue uptake, along with elevated free thyroid hormone and undetectable TSH levels); partial cure (normal free thyroid hormone and low/undetectable TSH levels); complete cure (normal thyroid hormone and TSH levels; restored extra nodular uptake). The patients were followed for up to 8.5 years (median 76 months). PEI therapy was well tolerated by all patients though a mild to moderate local pain occurred in about 30% of sessions. Complete cure was achieved in all pre-toxic patients and in 60 (70.6%) patients with toxic adenoma, while partial cure was observed in 11 cases (12.9%) and failure in 14 (16.5%). A significant shrinkage of nodule volume was observed in all patients (p = 0.0001), while those with toxic nodules larger than 30 mL showed a significantly lower response rate to PEI (p < 0.05). At controls, only one patient developed subclinical hypothyroidism while, among partially cured patients, five relapsed. The administration of methimazole and/or propranolol did not modify PEI outcome. In conclusion, we suggest that PEI therapy may be the treatment of choice in patients with pre-toxic thyroid adenoma where therapy is least necessary- despite the nodule volume. Though ethanol injection therapy of toxic thyroid nodules may be troublesome for the need of multiple sessions, it appears an effective alternative procedure in patients at poor surgical risk, and in younger patients in whom radioiodine is contraindicated. Since a special technical skill in intervention procedures is required, PEI therapy may be suitable only for patients living nearby a trained centre.

Is laparoscopic sonography a reliable and sensitive procedure for staging colorectal cancer? A comparative study.

BACKGROUND: Laparoscopic colectomy has developed rapidly with the explosion of technology. In most cases, laparoscopic resection is performed for colorectal cancer. Intraoperative staging during laparoscopic procedure is limited. Laparoscopic ultrasonography (LUS) represents the only real alternative to manual palpation during laparoscopic surgery. METHODS: We evaluated the diagnostic accuracy of LUS in comparison with preoperative staging and laparoscopy in 33 patients with colorectal cancer. Preoperative staging included abdominal US, CT, and endoscopic US (for rectal cancer). Laparoscopy and LUS were performed in all cases. Pre- and intraoperative staging were related to definitive histology. Staging was done according to the TNM classification. RESULTS: LUS obtained good results in the evaluation of hepatic metastases, with a sensitivity of 100% versus 62.5% and 75% by preoperative diagnostic means and laparoscopy, respectively. Nodal metastases were diagnosed with a sensitivity of 94% versus 18% with preoperative staging and 6% with laparoscopy, but the method had a low specificity (53%). The therapeutic program was changed thanks to laparoscopy and LUS in 11 cases (33%). In four cases (12%), the planned therapeutic approach was changed after LUS alone. CONCLUSIONS: The results obtained in this study demonstrate that LUS is an accurate and highly sensitive procedure in staging colorectal cancer, providing a useful and reliable diagnostic tool complementary to laparoscopy.

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients.

UNLABELLED: Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN). OBJECTIVE: In this study we have defined the long-term efficacy and safety of PEI for the treatment of ATN, and we have attempted to optimize the clinical usefulness and improve the technical approach to PEI treatment. PATIENTS: One hundred and seventeen patients with ATN, 26 males and 91 females, aged 48 +/- 12.9 years (mean +/- SD), were offered PEI when other established treatments were refused or contraindicated. Seventy-seven patients were affected by toxic adenoma (60 with a single nodule, 17 with a multinodular goitre); 40 patients suffered from a pretoxic single nodule. METHODS: Sterile 95% ethanol was administered weekly under sonographic control by a 20-22 gauge needle without anaesthesia or pharmacological sedation. During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. According to hormone and scintigraphic data, three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra-nodular tissue uptake, along with elevated free T4 (FT4) and free T3 (FT3) and undetectable TSH levels); partial cure (normalization of FT4 and FT3 levels, with low/ undetectable TSH levels; persistent suppression of extra-nodular uptake); complete cure (normal thyroid hormone and TSH levels; restored extra-nodular uptake). RESULTS: The patients were followed for up to 5 years (median 2.5). PEI therapy was well tolerated by all patients. Complete cure was achieved in all pretoxic patients and in 60 (77.9%) patients with toxic adenoma, while partial cure was observed in 7 cases (9.1%) and failure in 10 (13%). PEI treatment proved similarly effective in toxic patients with a single nodule or with multinodular goitre (87 vs 88.2%, respectively). At the end of treatment, a significant shrinkage of nodule volume was observed in all patients (P = 0.0001). Toxic patients with pretreatment volume > 40 ml (n = 8) did not show a significant difference in treatment response rate as compared to those with volume < 40 ml. Recurrence of hyperthyroidism was never observed during follow-up, independently of thyroid status before treatment. Only one patient with significant thyroid autoantibody serum levels before PEI treatment, developed sub-clinical hypothyroidism at 3 years. The administration of methimazole and/or propranolol did not modify PEI outcome. CONCLUSION: Our data confirm the efficacy and safety of percutaneous ethanol injection for the therapy of autonomous thyroid nodules. The very low incidence of hypothyroidism along with the absence of recurrence of hyperthyroidism suggests that percutaneous ethanol injection is the treatment of choice in patients with pretoxic thyroid adenoma. Percutaneous ethanol injection appears an effective alternative procedure in toxic patients with a high surgical risk even if they have large nodules, and in younger ones in whom radioiodine is contraindicated. Patients may be submitted to anti-thyroid drug and/or beta-blocker therapy if it is necessary, but this does not affect percutaneous ethanol injection treatment outcome. Finally, not only single autonomous thyroid nodules but also toxic multinodular goitre may be successfully treated by percutaneous ethanol injection.

Is percutaneous ethanol injection a useful alternative for the treatment of the cold benign thyroid nodule? Five years' experience.

We describe our 5-year experience with percutaneous ethanol injection (PEI) for the treatment of cold benign thyroid nodules and report its efficacy and side effects. Fifty-four euthyroid outpatients (aged 44.8+/-12.7 years, mean+/-SD) were divided into two groups matched for sex, age, and nodule volume: 27 patients treated only by PEI and 27 patients treated additionally with levothyroxine-suppressive therapy (median follow-up: 24 months, range 6-48). Mean pretreatment nodule volume was 21.0 mL (range 5.4-54.6). Ethanol (1.3+/-0.6 mL/mL nodule volume) was injected under sonographic control in 4 to 13 weekly sessions (mean 7.4). PEI therapy was well tolerated by all patients. At the end of treatment, nodule volume was 7.7+/-5.7 mL (p = .0001). A further significant shrinkage was obtained at 1-year follow-up (4.4+/-3.8 mL; p < .05). No significant differences in nodule reduction were observed between the levothyroxine treated or untreated group and between patients with pretreatment nodule volume smaller or larger than 15 mL. Our study confirms the efficacy and safety of PEI in inducing volume shrinkage of cold benign thyroid nodules. Overall our data suggest that PEI may become an interesting alternative for patients with surgical indications, if they refuse surgery or are poor surgical risks, or eventually demand treatment for aesthetic purposes. It may also be considered when levothyroxine therapy is contraindicated or ineffective.

Intrasplenic posttraumatic pseudoaneurysm: echo color doppler diagnosis.

Nonsurgical conservative treatment of blunt splenic trauma has gained widespread consensus in the last few years. It has been demonstrated that 60% of patients with blunt abdominal trauma with spleen lesion achieve the best therapy by using conservative therapy. Despite the accuracy of ultrasonography (US) and computed tomography in detecting and grading the spleen lesions, the evolution of the lesion is often unexpected. In 15 to 30% of patients, a two-stage splenic rupture may be expected within 2 weeks. Delayed complications, such as splenic abscesses and pseudoaneurysms of the splenic artery and its branches, have been observed. To prevent complications, a short follow-up has been scheduled for these patients by using US and US color Doppler. The authors propose routine echo Doppler evaluation for all patients affected by intraparenchymal hematoma after blunt abdominal trauma.

Omeprazole versus ranitidine plus somatostatin in the treatment of severe gastroduodenal bleeding: a prospective, randomized, controlled trial.

In a randomized, controlled clinical trial omeprazole was compared with ranitidine plus somatostatin in the treatment of severe acute gastrointestinal bleeding due to peptic pathology. Intravenous infusion of the drugs was administered until clinical stabilization or surgical operation. The two regimens were equally effective in controlling bleeding. The need for blood transfusion and surgical operation together with the mortality rate did not differ significantly between groups. No toxic effects were observed as a result of the infusion of omeprazole. In this study the infusion of omeprazole alone showed an efficacy comparable to the association of ranitidine and somatostatin in the treatment of severe acute peptic bleeding.