Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

The Natural Estrogen Receptor Beta Agonist Silibinin as a Promising Therapeutic Tool in Diffuse Large B-cell Lymphoma.

BACKGROUND/AIM: About 40% of patients with diffuse large cell lymphoma (DLBCL) still have a poor prognosis. Additionally, DLBCL patients treated with doxorubicin are at risk of cardiac failure. Growing evidence suggests an antitumor and cardioprotective activity exerted by estrogen via its binding to estrogen receptor (ER) ß. The aim of this study was to evaluate the anticancer activity of the phytoestrogen silibinin, an ERß selective agonist, on DLBCL growth, and its potential cardioprotective effect. MATERIALS AND METHODS: DLBCL cell lines SUDHL-8, SUDHL-6, and RIVA were used. The anti-tumor activity of silibinin was also evaluated in vivo in NOD/SCID/IL2Rg-/- (NSG) xenografted mice. AC16 human ventricular cardiomyocytes were used to investigate the cardioprotective effects of silibinin. RESULTS: In vitro silibinin induced apoptosis and autophagy, and blocked tumor cell proliferation, also protecting AC16 cardiomyocytes from doxorubicin-induced toxicity. In vivo silibinin induced cell death and autophagy, and reduced tumor volume. CONCLUSION: Silibinin represents a promising therapeutic tool.

On the role of sphingolipids in cell survival and death.

Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite several fundamental subcellular signaling processes but, more in general, they directly contribute to key biological activities such as cell motility, growth, senescence, differentiation as well as cell fate, i.e., survival or death. The sphingolipid metabolic pathway displays an intricate network of reactions that result in the formation of multiple sphingolipids, including ceramide, and sphingosine-1-phosphate. Different sphingolipids, that have key roles in determining cell fate, can induce opposite effects: as a general rule, sphingosine-1-phosphate promotes cell survival and differentiation, whereas ceramide is known to induce apoptosis. Furthermore, together with cholesterol, sphingolipids also represent the basic lipid component of lipid rafts, cholesterol- and sphingolipid-enriched membrane microdomains directly involved in cell death and survival processes. In this review, we briefly describe the characteristics of sphingolipids and lipid membrane microdomains. In particular, we will consider the involvement of various sphingolipids per se and of lipid rafts in apoptotic pathway, both intrinsic and extrinsic, in nonapoptotic cell death, in autophagy, and in cell differentiation. In addition, their roles in the most common physiological and pathological contexts either as pathogenetic elements or as biomarkers of diseases will be considered. We would also hint how the manipulation of sphingolipid metabolism could represent a potential therapeutic target to be investigated and functionally validated especially for those diseases for which therapeutic options are limited or ineffective.

Educational impact of hand motion analysis in the evaluation of FAST examination skills.

PURPOSE: Increasing pressure pushes towards the objective competence assessment of clinical operators. Hand motion analysis (HMA) was introduced to measure surgical and clinical procedures; its recent application to FAST examinations leaves unsolved issues. This study aimed at determining optimal HMA parameters to discriminate between operators' skill levels, and which FAST tasks are experience-dependent. METHODS: Ten experienced (EG) and 13 beginner (BG) sonographers performed a FAST examination on one female and one male model. A motion capture system returned the duration, working volume, number of movements (absolute and time normalized), and hand path length (absolute and time normalized) of each view. RESULTS: BG took more time in completing specific views, with a higher working volume (p = 0.003) and longer hands path (p < 0.001). The number of movements was lower in the EG (p < 0.001) and differed between views (p = 0.014). No significant Group/Model differences were found for the normalized number of movements. The LUQ view required a higher number of movements (p < 0.001). CONCLUSIONS: HMA identified kinematic parameters discriminating between proficiency level and critical subtasks in the FAST examination. These findings could be the base for a focused HMA-based evaluation of performances following a proctored training period. There is room to incorporate HMA into simulation metrics and evidence-based credentialing standards for clinical ultrasound applications.

Not only FAST The MUSEC® experience in training surgeons.

For a long time surgeons have been discussing the need to improve their skills in the use of ultrasound (US). However in the recent years it has become evident the importancxe for general aklnd trauma surgeons treating critically-ill patients to learn basic and advanced US. The two last editions (9th and 10th) of the ATLS manual have officially included FAST and e-FAST in the primary assessment of trauma patients, making this tool an essential skill for surgeons. In the acute care setting FAST, e-FAST and other applications have gained a pivotal, evidence-based role in this fields. Nevertheless, surgeons are rarely performing US exams by themselves, losing a major decision-making tool. The Modular Ultrasound ESTES Course (MUSEC®) was developed to provide both fundamental and advanced US training for surgeons in trauma and acute care settings. We are strongly convinced, in the light of the results from both the surveys carried out and the customer satisfaction tests administered to all the participants in the MUSEC courses, that US courses such as these should be part of the general surgery residency programs. KEY WORDS: e-FAST, MUSEC Ultrasound in Emergency Department, Ultrasound Training Trauma Patients.

Inflammatory cytokines associated with cancer growth induce mitochondria and cytoskeleton alterations in cardiomyocytes.

Cardiac dysfunction is often observed in patients with cancer also representing a serious problem limiting chemotherapeutic intervention and even patient survival. In view of the recently established role of the immune system in the control of cancer growth, the present work has been undertaken to investigate the effects of a panel of the most important inflammatory cytokines on the integrity and function of mitochondria, as well as of the cytoskeleton, two key elements in the functioning of cardiomyocytes. Either mitochondria features or actomyosin cytoskeleton organization of in vitro-cultured cardiomyocytes treated with different inflammatory cytokines were analyzed. In addition, to investigate the interplay between tumor growth and cardiac function in an in vivo system, immunocompetent female mice were inoculated with cancer cells and treated with the chemotherapeutic drug doxorubicin at a dosing schedule able to suppress tumor growth without inducing cardiac alterations. Analyses carried out in cardiomyocytes treated with the inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), interleukin 6 (IL-6), IL-8, and IL-1ß revealed severe phenotypic changes, for example, of contractile cytoskeletal elements, mitochondrial membrane potential, mitochondrial reactive oxygen species production and mitochondria network organization. Accordingly, in immunocompetent mice, the tumor growth was accompanied by increased levels of the inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8, either in serum or in the heart tissue, together with a significant reduction of ventricular systolic function. The alterations of mitochondria and of microfilament system of cardiomyocytes, due to the systemic inflammation associated with cancer growth, could be responsible for remote cardiac injury and impairment of systolic function observed in vivo.

Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis.

The role of autophagy in cancer onset and progression appears still controversial. On one hand, autophagy allows cancer cell to survive in unfavorable environmental conditions, on the other hand, once internal energy resources are exhausted, it leads to cell death. In addition, autophagy interpheres with cell cycle progression, de facto exerting a cytostatic activity. Hence, it represents an important target for anticancer therapy. For example, temozolomide (TMZ), of use for glioblastoma (GBM) treatment, appears as capable of inducing autophagy partially inhibiting cancer cell proliferation. However, GBM, a very aggressive brain tumor with poor prognosis even after surgery and radio-chemotherapy, invariably recurs and leads to patient death. Since cancer stem cells have been hypothesized to play a role in refractory/relapsing cancers, in the present work we investigated if autophagy could represent a constitutive cytoprotection mechanism for glioblastoma stem-like cells (GSCs) and if the modulation of autophagic process could affect GBM growth and survival. Thus, in the present study we first evaluated the relevance of autophagy in GBM tumor specimens, then its occurrence in GSCs and, finally, if modulation of autophagy could influence GSC response to TMZ. Our results suggested that, in vitro, the impairing autophagic process with quinacrine, a compound able to cross the blood-brain barrier, increased GSC susceptibility to TMZ. Death of GSCs was apparently due to the iron dependent form of programmed cell death characterized by the accumulation of lipid peroxides called ferroptosis. These results underscore the relevance of the modulation of autophagy in the GSC survival and death and suggest that triggering of ferroptosis in GSCs could represent a novel and important target for the management of glioblastoma.

Preclinical models in the study of sex differences.

The biology of sex differences deals with the study of the disparities between females and males and the related biological mechanisms. Gender medicine focuses on the impact of gender and sex on human physiology, pathophysiology and clinical features of diseases that are common to women and men. The term gender refers to a complex interrelation and integration of sex-as a biological and functional determinant-and psychological and cultural behaviours (due to ethnical, social or religious background). The attention to the impact of gender differences on the pathophysiology and, therefore, on the clinical management of the most common diseases, such as cardiovascular diseases (CVD), neurodegenerative disorders, immune and autoimmune diseases as well as several tumours, is in fact often neglected. Hence, studies covering different fields of investigation and including sex differences in the pathogenesis, in diagnostic and prognostic criteria as well as in response to therapy appear mandatory. However, prerequisites for this development are preclinical studies, including in vitro and in vivo approaches. They represent the first step in the development of a drug or in the comprehension of the pathogenetic mechanisms of diseases, in turn a necessary step for the development of new or more appropriate therapeutic strategies. However, sex differences are still poorly considered and the great majority of preclinical studies do not take into account the relevance of such disparities. In this review, we describe the state of the art of these studies and provide some paradigmatic examples of key fields of investigation, such as oncology, neurology and CVD, where preclinical models should be improved.

AMBRA1 and SQSTM1 expression pattern in prostate cancer.

Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions. The data reported in this pilot study demonstrated an increased expression of AMBRA1 and SQSTM1, which were also associated with an accumulation of LC3II in prostate cancer but not in benign lesion. In the present study we found that: (i) at variance with benign lesion, prostate cancer cells underwent SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but, also, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively correlated with the Gleason score. These results underscore a possible implication of autophagy in prostate cancer phenotype and of AMBRA1 as possible cancer progression biomarker in this malignancy.

Antioxidants counteract lipopolysaccharide-triggered alterations of human colonic smooth muscle cells.

Gut dysmotility develops in individuals during and after recovering from infective acute gastroenteritis and it is apparently due to a direct effect of circulating lipopolysaccharides (LPS). This is an endotoxin with a prooxidant activity derived from gram-negative bacteria. Due to the lack of human models available so far, the mechanisms underlying LPS-induced gut dysmotility are, however, poorly investigated. In the present work long-term effects of LPS and their reversibility have been assessed by means of different analytical cytology methods on pure primary cultures of human colonic smooth muscle cells. We found that LPS triggered the following alterations: (i) a redox imbalance with profound changes of contractile microfilament network, and (ii) the induction of cell cycle progression with dedifferentiation from a contractile to a synthetic phenotype. These alterations persisted also after LPS removal. Importantly, two unrelated antioxidants, alpha-tocopherol and N-acetylcysteine, were able to reverse the cytopathic effects of LPS and to restore normal muscle cell function. The present data indicate that LPS is capable of triggering a persistent and long-term response that could contribute to muscle dysfunction occurring after an infective and related inflammatory burst and suggest a reappraisal of antioxidants in the management of postinfective motor disorders of the gut.

Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington's disease.

Huntington's disease (HD) is a genetic neurodegenerative disease characterized by an exceedingly high number of contiguous glutamine residues in the translated protein, huntingtin (Htt). The primary site of cell toxicity is the nucleus, but mitochondria have been identified as key components of cell damage. The present work has been carried out in immortalized lymphocytes from patients with HD. These cells, in comparison with lymphoid cells from healthy subjects, displayed: i) a redistribution of mitochondria, forming large aggregates; ii) a constitutive hyperpolarization of mitochondrial membrane; and iii) a constitutive alteration of mitochondrial fission machinery, with high apoptotic susceptibility. Moreover, mitochondrial fission molecules, e.g., protein dynamin-related protein 1, as well as Htt, associated with mitochondrial raft-like microdomains, glycosphingolipid-enriched structures detectable in mitochondria. These findings, together with the observation that a ceramide synthase inhibitor and a raft disruptor are capable of impairing the peculiar mitochondrial remodeling in HD cells, suggest that mitochondrial alterations occurring in these cells could be due to raft-mediated defects of mitochondrial fission/fusion machinery.

Total or partial anatomical resection of segment 8 using the ultrasound-guided finger compression technique.

BACKGROUND: A new surgical technique to define intra-operatively segmental and subsegmental areas of the liver using ultrasound-guided bimanual liver compression has been recently described. However, this technique does not allow disclosure of the subsegmental ventral (S8v) and dorsal (S8d) portions of segment 8 (S8). Another technique that overcomes these limitations is described. METHODS: Six patients with hepatoma, cirrhosis and no evidence of portal vein thrombosis were submitted to the procedure. Demarcation of the resection area was achieved using ultrasound-guided finger compression of the S8 subsegmental portal branches (P8v and P8d). RESULTS: The procedure was feasible in all patients and demarcation was always obtained within 1 min of bimanual ultrasound-guided compression. In one patient, the entire S8 was resected. In the remaining five patients, the dorsal (four patients) or the ventral (one patient) portion was removed, respectively. There was no mortality or morbidity and no blood transfusions were administered. CONCLUSIONS: Disclosure of the subsegmental portions of S8 using the ultrasound-guided compression technique was feasible, safe and effective, and represents the completion of the ultrasound-guided compression technique for performing segmental and subsegmental anatomical resection of the liver.

Radiological estimation of size in colorectal liver metastases: is it reliable? Comparison with post-resectional measurements.

Since the efficiency of percutaneous ablation techniques in treating colorectal liver metastases is dependent on tumor size, the aim of this study was to verify the accuracy of computed tomography or magnetic resonance in estimating the maximum diameter of colorectal liver metastases by comparing these findings with those of pathology in a series of patients who underwent liver resection. Radiological and pathological tumor measurements in 39 patients operated for 69 colorectal liver metastasis were recorded. The radiological measurement was performed by magnetic resonance in 40 tumors (23 cases) and by computed tomography in 29 tumors (16 patients). The mean difference between pathological and radiological sizes was 0.4 cm (p < 0.001). Radiological size was smaller than pathological size in 60.9% of tumors, equal in 16% and bigger in 23% of tumors. The results indicated that radiology significantly underestimates the diameter of liver metastasis. To avoid on-site recurrence after percutaneous ablation therapies due to inaccurate radiological measurement, a radiological size of colorectal metastasis up to 2.5 cm should be considered as selection criteria for this treatment.

Ultrasound guided liver resection: does this approach limit the need for portal vein embolization?

BACKGROUND/AIMS: Major hepatectomy is associated with higher risks of morbidity and mortality. Portal vein embolization (PVE) has been advocated to minimize those risks. However, PVE itself has associated drawbacks. The use of ultrasound-guided liver resection minimizes the need for major resection, and might reduce the use of PVE. The aim of this study was to validate this hypothesis. METHODOLOGY: Two hundred and ninety-eight consecutive patients who underwent liver surgery were reviewed. Eighty-five of these patients with tumors corresponding to right 1st/2nd order portal branches (Zone P) and right hepatic vein (Zone H) were selected as potential candidates for major hepatectomy and PVE. Indications to PVE were based on the most recent reported criteria. Surgical strategy was based on the relationship between the tumor and the intrahepatic vascular structures at intraoperative ultrasonography (IOUS). RESULTS: Thirty-six (42%) patients with tumors located in Zones H and P were potential candidates to PVE, but none underwent this procedure. Major hepatecomies were performed in 10 (12%) patients. No hospital mortality was seen. Morbidity rate was 19% and major morbidity occurred in 2 patients. Blood transfusion rate was 12%. Mean tumor-free margin was 0.1 cm (median 0.1; range 0-0.6). None had local recurrence after a mean follow-up of 28 months (median 27; range 6-68). CONCLUSIONS: IOUS guidance allows an alternative, safe, and effective surgical approach for patients generally submitted to major hepatectomy and most of them to preoperative PVE. In this perspective, further studies are required to reassess indications to PVE.

One-stage ultrasonographically guided hepatectomy for multiple bilobar colorectal metastases: a feasible and effective alternative to the 2-stage approach.

BACKGROUND: Two-stage hepatectomy with or without portal vein embolization allows treatment of multiple bilobar metastases, thereby expanding operative indications for these patients. Two operations are needed, however, and some patients are not able to complete the treatment strategy because of disease progression. Using experience gained from our policy of ultrasonographically guided resection, we explored the safety and effectiveness of 1-stage operative procedures in patients otherwise recommended for the 2-stage approach. METHODS: A total of 29 patients with multiple (>or=4) bilobar colorectal liver metastases (CLM) were selected from 100 consecutive patients submitted to surgical resection. The total number of preoperative CLM was 163 (median, 5; range, 2-20). The operative strategy was based on tumor-vessel relationships at intraoperative ultrasonography (IOUS) and on findings at color Doppler IOUS. RESULTS: There was no in-hospital mortality. Tumor removal was feasible with 1-stage operative procedures in all but 3 patients who underwent laparotomy. The overall morbidity rate was 23% (6/26); none of the patients required reoperation. Major morbidity occurred in 1 patient (4%). Blood transfusions were administered in 4 patients (15%). After a mean follow-up of 17 months (median, 14; range, 6-54), 3 patients had died from systemic recurrence, 12 patients were alive without disease, and 11 were alive with disease. No local recurrences were observed at the resection margin. CONCLUSION: IOUS-guided resection based on strict criteria allows a 1-stage operative treatment in selected patients with multiple bilobar CLM. This strategy decreases the need for a two-stage hepatectomy, thereby avoiding the disadvantages of a 2-stage approach.

Hepatectomy for stage B and stage C hepatocellular carcinoma in the Barcelona Clinic Liver Cancer classification: results of a prospective analysis.

HYPOTHESIS: Using an algorithm for selection of patients with hepatocellular carcinoma (HCC) for surgery, Barcelona Clinic Liver Cancer (BCLC) classification stage B and stage C disease is not a contraindication. DESIGN: Prospective cohort study. SETTING: University tertiary care hospital. PATIENTS: Among 163 consecutive patients with HCC, 120 (73.6%) underwent surgery; 113 of 120 (94.2%) underwent resection. Of 113 patients, 61 (54.0%) had BCLC stage 0 or A disease, 24 (21.2%) had stage B disease, and 28 (24.8%) had stage C disease. INTERVENTIONS: Surgical strategy was based on the relationship of the tumor to the intrahepatic vascular structures on intraoperative ultrasonography. MAIN OUTCOME MEASURES: Mortality, morbidity, rate of cut edge local recurrences, and long-term outcome were evaluated. P < .05 was considered statistically significant. RESULTS: Hospital mortality was 0.9%. The overall morbidity was 27.4%, and major morbidity was 3.5%. After a median follow-up of 24 months (range, 1-65 months), there was no cut edge recurrence. For patients with BCLC stages 0 or A, B, and C disease, the 3-year overall survival rates were 81%, 67%, and 74%, respectively (P =.24); the 3-year disease-free survival rates were 30%, 35%, and 15%, respectively (P =.85); and the 3-year hepatic disease-free survival rates were 39%, 44%, and 17%, respectively (P =.79). CONCLUSIONS: Patients with BCLC stage B and stage C HCC can tolerate hepatic resection with low mortality, acceptable morbidity, and survival benefits if resection is performed under strict intraoperative ultrasonographic guidance. These results should prompt revision of the BCLC recommendations.

Monopolar floating ball versus bipolar forceps for hepatic resection: a prospective randomized clinical trial.

BACKGROUND: Hepatic transection by Pean-clasia is the mainstream technique that can be used with different coagulators. Monopolar floating ball (MFB) is proposed for liver transection. Whether its value for liver transection is unclear, its efficiency as a coagulator only seems high. We compared in a prospective randomized study the standard Pean-clasia with bipolar forceps (BF) versus Pean-clasia with MFB in patients undergoing hepatic resection. METHODS: Seventy-six patients scheduled for hepatectomy were randomized in two groups, according to the coagulator device: group A (MFB, n = 38) and group B (BF, n = 38). The two groups were homogeneous in terms of tumor presentation and background liver features. Blood loss, blood transfusions, transection time, number of ligatures, drain discharge, drain bilirubin levels at third, fifth, and seventh postoperative day, and postoperative morbidity and mortality were prospectively evaluated. RESULTS: No significant differences between groups A and B were seen in terms of blood transfusions (11.5% versus 16.5%; p = 0.450), blood loss/cm(2) (mean 7.2 versus 7.6 ml; p = 0.450), transection time/cm(2) (mean 2.1 versus 2.3; p = 0.070), number of ligatures/cm(2) (mean 0.7 versus 0.7; p = 1), drain discharge (mean 55 versus 66.7 ml; p = 0.451), and drain bilirubin levels (mean 1.9 versus 2.1 mg/dl; p = 0.664). No mortality or major morbidity was recorded in both groups. CONCLUSIONS: This study showed that association of Pean-clasia with MFB was safe and minimized the blood loss during hepatic resection. However, MFB did not offer significant benefits over BF, while its cost is not negligible.

Systematic extended right posterior sectionectomy: a safe and effective alternative to right hepatectomy.

BACKGROUND: A surgical approach based on ultrasound-guided hepatectomy might minimize the need for major resection, whose rates of morbidity and mortality are not negligible. Right hepatectomy (RH) is traditionally performed in cases of vascular invasion of the right hepatic vein with multiple tumors in the right posterior section, and/or of the right posterior portal branch (P6-7) with tumor in contact with right anterior portal branch (P5-8). We herein describe an alternative approach to RH consisting in ultrasound-guided systematic extended right posterior hepatic sectionectomy (SERPS). METHODS: Among 207 consecutive patients who underwent hepatectomies, 21 (10%) underwent SERPS. Median age was 67 years (range, 48-79). There were 13 men and 8 women. Ten (48%) patients had hepatocellular carcinoma; 11 (52%) had colorectal liver metastases. Median tumor number was 2 (range, 1-15); median tumor size was 4.5 cm (range, 2.5-20). Ten (48%) patients had cirrhosis, 8 (38%) had steatosis, and 3 (16%) had normal liver. Surgical strategy was based on tumor-vessels relationship at intraoperative ultrasonography (IOUS) and on findings at color-Doppler IOUS. RESULTS: In-hospital and 90-days mortality were nil. Major and minor morbidity occurred in 3 (14%) and 2 (9.5%) patients, respectively. No patients were reoperated because of complications. Blood transfusions were given to 2 (9.5%) patients. After a median follow-up of 21 months, no local recurrence was observed. CONCLUSIONS: IOUS-guided SERPS is feasible, safe, and effective. It should be applied whenever possible as alternative resection to RH to maximize liver parenchymal sparing.

Contrast-enhanced intraoperative ultrasonography during surgery for hepatocellular carcinoma in liver cirrhosis: is it useful or useless? A prospective cohort study of our experience.

BACKGROUND: Preliminary results showed that contrast-enhanced intraoperative ultrasonography (CEIOUS) could provide information not obtainable with conventional IOUS during surgery for hepatocellular carcinoma (HCC). The aim of the study was to prospectively validate the role of CEIOUS on the basis of a larger experience and to establish a new classification that takes into account its findings. METHODS: Eighty-seven consecutive patients underwent hepatecomies for HCC. Those patients with new lesions at IOUS underwent CEIOUS: for that patients received intravenously 4.8 mL sulphurhexafluoride microbubbles. Pattern of enhancement was classified in 4 categories: A1 (full enhancement in the arterial phase and wash-out in the delayed phases), A2 (intralesional signs of neovascularization during all phases), A3 (no nodular enhancement but detectability during the liver enhancement), and B (undetectability during the liver enhancement). Resection was recommended for A1-3 nodules and no treatment for B nodules. RESULTS: Twenty-nine patients (33%) had 59 new lesions at IOUS and underwent CEIOUS. Twenty-seven nodules showed a B pattern at CEIOUS and were not removed; 32 nodules were classified as A1 in 5 patients, A2 in 11 patients, and A3 in 16 patients. The nodules were removed, and by histology, five A1, nine A2, and six A3 nodules were confirmed to be HCC. CEIOUS modified the operative decision making in 79% of these patients. CONCLUSIONS: CEIOUS is useful during surgery for HCC; it complements the accuracy of IOUS and affects the radicalness of the surgical. Specificity of CEIOUS has to be further improved, although intrinsic drawbacks exist in the diagnostic criterion of tumor vascularity.