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.

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.

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.

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.

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.

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.

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.

The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?

BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). METHODS: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. RESULTS: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.