Appendiceal collision tumors: case reports, management and literature review.

Appendiceal tumors are incidentally detected in 0.5% cases of appendectomy for acute appendicitis and occur in approximately 1% of all appendectomies. Here, we report two cases of appendiceal collision tumors in two asymptomatic women. In both cases, imaging revealed right-lower-quadrant abdominal masses, which were laparoscopically resected. In both cases, histological examinations revealed an appendiceal collision tumor comprising a low-grade appendiceal mucinous neoplasm and well-differentiated neuroendocrine neoplasm (NEN). For complete oncological control, right hemicolectomy was performed in one patient for the aggressive behavior of NEN; however, histology revealed no metastasis. The other patient only underwent appendectomy. No further treatment was recommended. According to the latest guidelines, exact pathology needs to be defined. Proper management indicated by a multidisciplinary team is fundamental.

Robotic resection of a single adenoid cystic tumor liver metastasis using ICG fluorescence. A case report and literature review.

Adenoid cystic carcinoma (AdCC) is a rare tumor that typically develops in the salivary glands and less frequently in other sites of the head and neck region. Only a few cases of resected metachronous liver metastases have been reported. Minimally invasive surgery is currently the gold standard of care for liver resections; furthermore, the use of Indocyanine Green (ICG) is continuously increasing in surgical practice, especially in cases of primary liver tumors and colorectal liver metastases, due to its capacity to enhance liver nodules. We report the case of a 54-year-old male with a single liver metastasis of AdCC, located in SIII, who presented in our center 9 months after resection of a primary tumor of the laryngotracheal junction and adjuvant proton therapy. A 25-mg injection of ICG (0.3 mg/kg) was administered 48 h before surgery in order to highlight the tumor and perform an ICG-guided resection. The lesion was clearly visible during surgery, and, given its position and the proximity to the main lobar vessels of the left lobe, we opted for a left lateral sectionectomy. The outcome was unremarkable, with no major postoperative complications. The administration of ICG 48 h before surgery seems to be a valid tool even in cases of AdCC liver metastases, providing surgeons with better visualization of the lesion and improving the precision of the resection.

Inferior Mesenteric Artery Ligation Level in Rectal Cancer Surgery beyond Conventions: A Review.

Within the intricate field of rectal cancer surgery, the contentious debate over the optimal level of ligation of the inferior mesenteric artery (IMA) persists as an ongoing discussion, influencing surgical approaches and patient outcomes. This narrative review incorporates historical perspectives, technical considerations, and functional as well as oncological outcomes, addressing key questions related to anastomotic leakage risks, genitourinary function, and oncological concerns, providing a more critical understanding of the well-known inconclusive evidence. Beyond the dichotomy of high versus low tie, it navigates the complexities of colorectal cancer surgery with a fresh perspective, posing a transformative question: "Is low tie ligation truly reproducible?" Considering a multidimensional approach that enhances patient outcomes by integrating the surgeon, patient, technique, and technology, instead of a rigid and categorical statement, we argued that a balanced response to this challenging question may require compromise.

Anastomotic Leakage after Colorectal Surgery in Ovarian Cancer: Drainage, Stoma Utility and Risk Factors.

Objective: to evaluate the incidence of anastomotic leakage (AL), risk factors and utility of drainage and stoma in patients undergoing intestinal surgery for ovarian cancer in a single institution and in a review of the literature. Methods: retrospective study that includes consecutive patients undergoing debulking surgery with en bloc pelvic resection with rectosigmoid colectomy for ovarian cancer between 1 November 2011 and 31 December 2021. Data regarding patient and tumour characteristics, surgical procedure, hospitalisation, complications and follow-up were recorded and analysed. The PubMed database was explored for recent publications on this topic. Results: Seventy-five patients were enrolled in the study. All anastomoses were performed at a distance of >6 cm from the anal margin, with negative leak tests and tension-free anastomosis. Diverting stoma were performed in just three patients (4%). At least one perianastomotic pelvic drain was positioned in 71 patients (94.7%) and was removed on average on postoperative day 7. Four patients (5.3%) experienced AL. In all cases, the drain content was not the only sign of complication, as the clinical signs were also highly suggestive. Just one patient received conservative treatment. Average postoperative hospitalisation was 14.6 days (SD: ±9.7). There were no deaths at 30 and 60 days after surgery. Between the AL and non-AL groups, statistically significant differences were observed for age, Charlson Comorbidity Index, length of the intestinal resection and fitness for chemotherapy at 30 days. In ovarian cancer, rectosigmoid resection is a standardised procedure with comparable results for AL, and risk factors for AL are discretely homogeneous. What is neither homogeneous nor standardised according to the literature is the use of stomas and/or drains. Conclusion: use in the future of protective stoma and/or intra-abdominal drains is to be explored in selected and standardised situations to verify their preventive role.

The role of robotic surgery for the treatment of hilar cholangiocarcinoma: A systematic review.

Background: The role of robotic surgery (RS) for hilar cholangiocarcinoma (HC) is under investigation. Surgical resection is the only curative modality of treatment but extremely complex and high risk of morbidity and mortality may occur. The aim of this study is to perform a systematic review of perioperative and oncological outcomes of RS for HC, across a comprehensive range of outcomes reported in recent literature. Materials and Methods: PRISMA checklist was used as a basis for writing the systematic review and studies' selection. Literature documenting RS for HC was analyzed by searching PubMed and Cochrane Library from 2009 to May 2022. The search terms, either independently or in combination, were used according to PICOT framework. The target population are patients treated with robotic surgical approach for HC. Results: 12 studies with 109 patients were included after screening process. The Bismuth classification in all series except one was: 21 type I, 7 type II, 12 type IIIa, 26 type IIIb and 4 type IV. Mean operative time for a total of 21 patients was 644 minutes. Other two case series reported a median operative time of 375 with a console time of 276 minutes. Mean blood loss for case reports and two case series was 662 milliliters. Blood transfusion rate for all operation was 33.3%. Overall Conversion rate was 2.8%. Pooled post operative morbidity and mortality was 39.8% and 1.8% respectively. Mean LOS for case reports and one case series for a total of 17 patients was 16 days. R0 resection rate for the 11 papers was 74.3%. Seven out of 12 studies reported on the oncological follow up: median observation time ranged from 5 to 60 months, recurrence rate was 52.6% (range 0-90%) reported only in 19 patients (10/19). Conclusions: RS for HC was feasible and safe. However, although this systematic review could not be conclusive in most of the analyzed items, RS for the treatment of HC could represent the best tool for a future meticulous and precision surgery. The review's results certainly indicate that further research in urgently is required on this field.

Visceral adiposity is associated with worse urinary and sexual function recovery after radical prostatectomy: Results from a longitudinal cohort study.

OBJECTIVE: A prospective longitudinal cohort study on the impact of anthropometric measures on the sexual function and continence recovery in patients treated with laparoscopic radical prostatectomy (LRP) is presented. MATERIAL AND METHODS: Anthropometric measures, International Index of Erectile Function (IIEF-5) and International Prostatic Symptoms Score questionnaires, were collected before surgery and at the end of follow-up period. All patients were assigned into the following groups: A) non-obese; B) non-obese with central adiposity; C) obese without central adiposity; D) obese with central adiposity. Urinary and sexual functions were the outcome measures. RESULTS: At the end of follow-up, in 29 patients with visceral adiposity (VA) the median IIEF-5 was 14 (IQR 7-18) while in 49 non-VA patients (62.8%) was 22 (IQR 17-24) (p < 0.001). Twenty-three patients (79.3%) with VA reported complete continence, while 6 (20.7%) used ≥ 2 pads per day. Forty-eight patients (97.9%) without VA reported complete continence. VA was confirmed as a strong independent predictor for worse continence (HR 3.67; 2.75-4.51 CI95% p = 0.003) and sexual function recovery (HR: 4.51; 3.09-5.63 CI95% p < 0.001). CONCLUSION: We truly believe obese with visceral adiposity patients with prostate cancer should receive detailed preoperative counseling before surgery, including higher risk of suboptimal functional outcomes.

Abdominal wall complications after kidney transplantation: A clinical review.

INTRODUCTION: Abdominal wall complications are common after kidney transplantation, and although they have a minor impact on patient and graft survival, they increase the patient's morbidity and may have an impact on quality of life. Abdominal wall complications have an overall incidence of 7.7-21%. METHODS: This review will explore the natural history of abdominal wall complications in the kidney transplant setting, with a special focus on wound dehiscence and incisional herni, with a particular emphasis on risk factors, clinical characteristics, and treatment. RESULTS: Many patient-related risk factors have been suggested, including older age, obesity, and smoking, but kidney transplant recipients have an additional risk related to the use of immunosuppression. Wound dehiscence usually does not require surgical intervention. However, for deep dehiscence involving the fascial layer with concomitant infection, surgical treatment and/or negative pressure wound therapy may be required. CONCLUSIONS: Incisional hernia (IH) may affect 1.1-18% of kidney transplant recipients. Most patients require surgical treatment, either open or laparoscopic. Mesh repair is considered the gold standard for the treatment of IH, since it is associated with a low rate of postoperative complications and an acceptable rate of recurrence. Biologic mesh could be an attractive alternative in patients with graft exposition or infection.

The negative effects of COVID-19 and national lockdown on emergency surgery morbidity due to delayed access.

BACKGROUND: The aim of this retrospective comparative study was to assess the impact of COVID-19 and delayed emergency department access on emergency surgery outcomes, by comparing the main clinical outcomes in the period March-May 2019 (group 1) with the same period during the national COVID-19 lockdown in Italy (March-May 2020, group 2). METHODS: A comparison (groups 1 versus 2) and subgroup analysis were performed between patients' demographic, medical history, surgical, clinical and management characteristics. RESULTS: Two-hundred forty-six patients were included, 137 in group 1 and 109 in group 2 (p = 0.03). No significant differences were observed in the peri-operative characteristics of the two groups. A declared delay in access to hospital and preoperative SARS-CoV-2 infection rates were 15.5% and 5.8%, respectively in group 2. The overall morbidity (OR = 2.22, 95% CI 1.08-4.55, p = 0.03) and 30-day mortality (OR = 1.34, 95% CI 0.33-5.50, =0.68) were significantly higher in group 2. The delayed access cohort showed a close correlation with increased morbidity (OR = 3.19, 95% CI 0.89-11.44, p = 0.07), blood transfusion (OR = 5.13, 95% CI 1.05-25.15, p = 0.04) and 30-day mortality risk (OR = 8.00, 95% CI 1.01-63.23, p = 0.05). SARS-CoV-2-positive patients had higher risk of blood transfusion (20% vs 7.8%, p = 0.37) and ICU admissions (20% vs 2.6%, p = 0.17) and a longer median LOS (9 days vs 4 days, p = 0.11). CONCLUSIONS: This article provides enhanced understanding of the effects of the COVID-19 pandemic on patient access to emergency surgical care. Our findings suggest that COVID-19 changed the quality of surgical care with poorer prognosis and higher morbidity rates. Delayed emergency department access and a "filter effect" induced by a fear of COVID-19 infection in the population resulted in only the most severe cases reaching the emergency department in time.

The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: results from a phase IV study.

PURPOSE: To evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP). METHODS: Patients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use. RESULTS: Eighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; - 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [- 7938 UDD]. No clinically relevant adverse effects were reported. CONCLUSIONS: L. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use.

Clinical results of active scanning proton therapy for primary liver tumors.

BACKGROUND: Evidence for the efficacy of radiation therapy for primary liver cancer is growing. In this context, proton therapy (PT) can potentially improve the therapeutic ratio, as demonstrated by recent clinical studies. Here we report the first European clinical experience on the use of PT for primary liver cancer. METHODS: All patients treated for primary liver cancer in our center entered the analysis. Patients were simulated during deep expiration breath-hold. A 15-fraction treatment schedule was adopted using active scanning PT. Clinical outcome and toxicity were retrospectively analyzed. RESULTS: Between January 2018 and December 2019, 18 patients were treated. Fourteen patients had hepatocellular carcinoma (HCC), three patients had intrahepatic cholangiocarcinoma (ICC), and one patient had synchronous ICC-HCC. The Child-Pugh score was A5 in the majority of patients with HCC (71.4%). Median prescription dose was 58.05 Gy (range, 50.31-67.5). Median follow-up was 10 months (range, 1-19). The majority of deaths occurred from liver tumor progression. One-year overall survival (OS) was 63%. A significant correlation between worse OS and patient performance status, vascular invasion, and tumor stage was recorded. One-year local control was 90%. Toxicity was low, with a decrease in Child-Pugh score ⩾2 points detected in one patient. No cases of classic radiation-induced liver disease occurred. CONCLUSIONS: Our initial results of active scanning PT for primary liver cancer demonstrated the feasibility, safety, and effectiveness of this advanced technique in this setting. The potential of the combination of PT with other locoregional therapies is under evaluation.

Gastrointestinal tract injuries after thermal ablative therapies for hepatocellular carcinoma: A case report and review of the literature.

BACKGROUND: Radiofrequency ablation (RFA) and microwave ablation (MWA) represent the standard of care for patients with early hepatocellular carcinoma (HCC) who are unfit for surgery. The incidence of reported adverse events is low, ranging from 2.4% to 13.1% for RFA and from 2.6% to 7.5% for MWA. Gastrointestinal tract (GIT) injury is even more infrequent (0.11%), but usually requires surgery with an unfavourable prognosis. Due to its low incidence and the retrospective nature of the studies, the literature reporting this feared complication is heterogeneous and in many cases lacks information on tumour characteristics, comorbidities and treatment approaches. CASE SUMMARY: A 77-year-old man who had undergone extended right hepatectomy for HCC was diagnosed with early disease recurrence with a small nodule compatible with HCC in the Sg4b segment of the liver with a subcapsular location. He was treated with percutaneous RFA and a few week later he was urgently admitted to the Surgery ward for abdominal pain and fever. A subcutaneous abscess was diagnosed and treated by percutaneous drainage. A fistulous tract was then documented by the passage of contrast material from the gastric antrum to the abdominal wall. The oesophagogastroduodenoscopy confirmed a circular wall defect at the lesser curvature of gastric antrum, leading directly to the purulent abdominal collection. An over-the-scope clip (OTSC) was used to successfully close the defect. CONCLUSION: This is the first reported case of RFA-related GIT injury to have been successfully treated with an OTSC, which highlights the role of this endoscopic treatment for the management of this complication.

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis.

BACKGROUND: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. METHODS: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. RESULTS: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220-0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. CONCLUSIONS: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.

Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred.

BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal disease caused by inactivating germ-line mutations of HRPT2 gene, with subsequent loss of Parafibromin expression. It is characterized by familial HPT, ossifying jaw tumors, and other associated neoplasms. METHODS: Clinical, histopathological, and genetic features of three large Italian unrelated HPT-JT kindred were assessed. RESULTS: Three different germ-line HRPT2 inactivating mutations were identified. Seventeen affected members and six healthy mutation carriers were found. HPT was diagnosed in virtually all affected patients, at a median age of 36.3 years (range 11-71). In all cases, a single parathyroid involvement was found at surgery, although a metachronous multiglandular involvement causing recurrence after selective parathyroidectomy occurred in 17.6% of cases, after a mean disease-free interval of 13.7 years (range 5-27). Parathyroid carcinoma, atypical parathyroid adenoma, and jaw tumor occurred in one case; uterine involvement in 61.5% of women; other associated neoplasms were thyroid carcinoma (two cases) and renal and colon carcinoma (one case). Immunohistochemistry confirmed the loss of Parafibromin as the distinctive feature of the disease both in parathyroid and uterine tumors. CONCLUSIONS: HPT-JT has a frequent single-gland parathyroid involvement and a relatively increased risk of parathyroid carcinoma. The penetrance of the disease is high but incomplete. Regardless of the denomination of the syndrome, jaw tumors occur rarely, while uterine involvement is frequently present. Selective parathyroidectomy may be an effective strategy, but a prolonged follow-up is required because of the risk of recurrences and malignancies. A systematic investigation is also required because of associated malignancies.

Prospective validation of the Barcelona Clinic Liver Cancer staging system.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC's peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit. METHODS: One hundred and ninety-five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model. RESULTS: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend chi(2)=43.01, likelihood chi(2)=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients. CONCLUSIONS: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies.

Syngeneic living-donor liver transplantation for hemangioendothelioma: a clinical model for studying liver regeneration.

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Multimodal therapy before liver transplantation for hepatocellular carcinoma.

BACKGROUND: : The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. METHODS: : Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). RESULTS: : Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3-16 months). On histological examination, 42% of the group did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). CONCLUSIONS: : The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

Isoniazid-related fulminant hepatic failure in a child: assessment of the native liver's early regeneration after auxiliary partial orthotopic liver transplantation.

We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF.

Role of blood AFP mRNA and tumor grade in the preoperative prognostic evaluation of patients with hepatocellular carcinoma.

AIM: To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria. METHODS: Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies. RESULTS: At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables. CONCLUSION: The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.

Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical-pathological parameters remains controversial, however. METHODS: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. RESULTS: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months. CONCLUSIONS: Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors.

Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: a preliminary prospective study.

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.