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Background: The role of prophylactic primary tumor resection (PTR) in patients with small intestinal neuroendocrine tumors (SI-NETs) and unresectable liver metastases is a matter of debate., Objective: We aimed to evaluate outcomes in patients with SI-NETs who underwent PTR, according to the presence of metastasis and symptoms from primary., Material and Methods: Data from patients who underwent PTR for SI-NETs from a single referral center (2007-2023) were prospectively collected. Patients were divided into three groups: non-metastatic (M0) and metastatic with primary tumor-related symptoms (MS) or metastatic asymptomatic (MA). Kaplan-Meier curves for overall survival (OS) and event-free survival (EFS) were generated and compared by group. Univariate and multivariable Cox regression analyses were performed to assess the significance of risk factors., Results: Of 147 patients, 53 were M0, 23 were MS, and 71 were MA. Median follow-up was 26 months. The 5- and 10-year OS estimates were 100% and 100% in M0 patients, 82 and 21% in MS patients, and 89 and 80% in MA patients, respectively (p < 0.001). Median EFS was 91 months overall and 43,126 months and not reached for the MS, MA, and M0 groups, respectively (p < 0.001). In multivariable analysis, MS (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.71-9.52), functioning tumors (HR 1.98, 95% CI 1.03-3.81), and G2 grade (HR 3.20, 95% CI 1.64-6.85) were associated with a shorter EFS., Conclusions: In this large retrospective series, the MS group had a significantly worse OS and EFS compared with M0 and MA. This finding suggests that prophylactic PTR might benefit SI-NET patients with unresectable liver metastases, as symptom development could impair long-term prognosis after surgery., Competing Interests: DISCLOSURE: Maria Danieli, Uberto Fumagalli Romario, Davide Radice, Simonetta Pozzi, Francesca Spada, Luigi Funicelli, Nicola Fazio, and Emilio Bertani have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Importance: The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies., Objective: To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC., Design, Setting, and Participants: This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months)., Intervention: Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy., Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported., Results: Overall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects., Conclusions and Relevance: These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival., Trial Registration: ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

Radioligand therapy (RLT) with lutetium ( 177 Lu) oxodotreotide is an approved therapy in combination with somatostatin analogues (SSAs) for patients with advanced, well-differentiated G1-G2, gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) that progress on SSAs. We conducted a series of round table meetings throughout Italy to identify issues related to RLT delivery to patients with GEP-NETs. Four key issues were identified: (1) the proper definition of tumour progression prior to RLT initiation; (2) the impact of RLT in patients with bone metastases and/or high hepatic tumour burden; (3) the optimal follow-up protocol after RLT; and (4) organisational issues related to RLT use and managerial implications. This article reviews the literature relating to the aforementioned issues and makes recommendations based on available evidence and Italian NET experts' opinions. In particular, the group recommends the development of a diagnostic-therapeutic care pathway (DTCP) for patients undergoing RLT which provides systematic guidance but can still be individualised for each patient's clinical and psychosocial needs. A DTCP may clarify the diagnostic, therapeutic and post-treatment monitoring process, and improve communication and the coordination of care between hub and spoke centres. The DTCP may also contribute to changes in the care process related to the 2013/59/EURATOM Directive and to the definition of costs when planning for future or updated reimbursement of RLT in Italy., (© 2023. The Author(s).)

This study determines the oncologic outcome of the combined resection and ablation strategy for colorectal liver metastases. Between January 1994 and December 2015, 373 patients underwent surgery for colorectal liver metastases. There were 284 patients who underwent hepatic resection only (Group 1) and 83 hepatic resection plus ablation (Group 2). Group 2 patients had a higher incidence of multiple metastases (100% in Group 2 vs 28.2% in Group 1; P < 0.001) and bilobar involvement (76.5% in Group 2 vs 12.9% in Group 1; P < 0.001) than Group 1 cases. Perioperative mortality was nil in either group, with a higher postoperative complication rate among Group 1 versus Group 2 cases (18 vs 0, respectively). The median follow-up was 90 months (range, 1-180), with a five-year overall survival for Group 1 and Group 2 of 51 per cent and 80 per cent, respectively ( P = 0.193). Mean disease-free survival for patients with R 0 resection was 55 per cent, 40 per cent, and 37 per cent at one, two, and three years, respectively, and remained steadily higher (at 50%) in those patients treated with resection combined with ablation up to five years ( P = 0.069). The only intraoperative ablation failure was for a large lesion (≥5 cm). Our data support the use of intraoperative ablation when complete hepatic resection cannot be achieved.

Background: The role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients., Methods: From two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS)., Results: The two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the 18 FDG PET-CT and age. In the operated patients, surgical morbidity comprised 7 cases of pancreatic fistula. Postoperative mortality was nil. Median OS for patients undergoing left-pancreatectomy was 111 months vs 52 for the non operated patients (p = 0.003). At multivariate analysis after propensity score adjustment, no surgery as well as liver tumour burden>25% and higher Ki-67 index were associated with an increased risk of death during follow-up. In patients with unresectable primary tumour, OS was similar in comparison to that in the resectable but non-resected patients, and significantly worse than that in the resected patients (p = 0.032)., Conclusion: In PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery., Methods: From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS)., Results: Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048., Conclusions: Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.

The present study determines the oncologic outcome of the combined resection and ablation strategy for colorectal liver metastases (CRLM). Between January 1994 and December 2014, 360 patients underwent surgery for CRLM. There were 280 patients who underwent hepatic resection only (group 1) and 80 hepatic resection plus ablation (group 2). group 2 patients had a higher incidence of multiple metastases than group 1 cases (100% in group 2 vs. 28.2% in group 1; P<0.001) and bilobar involvement (76.5% in group 2 vs. 12.9% in group 1; P<0.001). Perioperative mortality was nil in either group with a higher postoperative complication rate amongst group 1 vs. group 2 cases (18 vs. 0, respectively). The median follow-up was 90 months (range, 1-180) with a 5-year overall survival for group 1 and group 2 of 49 and 80%, respectively (P=0.193). The median disease-free survival for patients with R0 resection was 50, 43 and 34% at 1, 2 and 3 years, respectively, and remained steadily higher (at 50%) in those patients treated with resection combined with ablation up to 5 years (P=0.069). The only intraoperative ablation failure was for a large lesion (≥5 cm). Our data support the use of intraoperative ablation when complete hepatic resection cannot be achieved.

Introduction: Patients with small intestine neuroendocrine tumors present with liver metastases in 50-75% of cases at diagnosis. The aim of the present study was to assess prognostic factors in patients with liver metastases from intestinal neuroendocrine tumor after primary tumor surgical removal with or without liver surgery or radiofrequency ablation. The primary endpoint was disease-specific survival., Methods: Data regarding seventy-eight consecutive patients with liver metastases who undergone primary tumor surgical removal between 1996 and 2011 were extracted from the institutional tumor registry and retrospectively analyzed., Results: Liver tumor burden was <25% in 43 (55.1%) 25-50% in 30 (38.5%) and >50% in 5 (6.4%) patients. For the whole cohort of patients disease-specific survival at 3, 5 and 8 years was 93.2%, 83.6% and 77.3%, respectively. Fifteen patients who underwent radical liver surgery were all alive with a median survival of 106 months (range 18-152 months). In multivariate analysis the Ki-67 index in a continuous fashion significantly correlate with prognosis (p = 0.021). Liver tumor burden (p = 0.036) and extrahepatic involvement (p = 0.03), were the most powerful prognosticators for patients who underwent only debulking surgery., Conclusion: The Ki-67 index, the liver tumor burden and the presence of extrahepatic metastases should be carefully considered in the selection criteria for liver debulking in asymptomatic patients., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC., Patients and Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed., Results: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001)., Conclusions: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

Background: Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of cases with liver metastases as the only systemic localization. Liver metastases are unresectable in 80% of cases at diagnosis. In the context of a metastatic disease, the benefit of primary tumor removal in terms of survival is controversial., Methods: A single-center series of patients with PNETs presenting with synchronous unresectable hepatic metastases and treated within a framework of a multidisciplinary team was analyzed retrospectively to assess the prognostic factors and the potential benefit of primary tumor resection on long-term survival., Results: At the time of diagnosis, 12 of 43 patients (28%) underwent primary tumor resection. After a median follow-up of 5 years (range, 0.6-14 years), 22 disease-related deaths were observed. The corresponding 5-year survival and median disease-specific duration of survival were 58% and 77 months, respectively. In the operated and nonoperated patients the 5-year disease-specific survival was 82% and 50%, respectively (P = .027). At multivariate analysis, patients with primary tumor removed had an improved survival compared with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other important factors associated with improved survival at multivariate analysis were lesser age, lesser Ki-67 index, and 25% less liver tumor burden., Conclusion: In the present series of patients with PNETs and unresectable liver metastases, resection of the primary tumor was associated with an improved survival. This observation suggests that resection of the primary tumor should be part of a global therapeutic strategy and its indication and timing should be discussed within a multidisciplinary team., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Among primary liver cancers occurring worldwide, hepatocellular carcinoma (HCC) is the major histological type accounting for 70-85% of all cases. Phase III trials in patients with advanced HCC treated with sorafenib (SO), a multitargeted tyrosine kinase inhibitor, showed significant improvements in both overall and progression-free survival. We report the cases of two elderly patients with advanced HCC who had prolonged stable disease following treatment with SO (400 mg bid). Patient 1 was treated with SO for a period of 16 months until evidence of right sacral metastases was noted. Patient 2 received SO 400 mg bid from January 2009 to October 2009 until radiological evidence of disease progression was noted. Both patients experienced minimal toxicity, suggesting that SO can be safely administered to elderly patients.

Objective: The objective of the study was to evaluate the role of perfusion computed tomography (CT) for monitoring and predicting therapy response in patients with hepatocellular carcinoma treated with thalidomide., Methods: Twenty-four patients with advanced hepatocellular carcinoma were treated with thalidomide. Perfusion and conventional CT were performed at baseline and every 2 months until disease progression. Baseline tumor size and enhancement characteristics, as well as baseline perfusion parameters and their changes after therapy, were explored and tested for association with therapy response., Results: Perfusion CT was feasible in 18 patients. Baseline tumor size and enhancement characteristics showed no predictive value, whereas baseline blood flow and blood volume were higher in patients with progressive disease (P < 0.042), with cutoff values for blood flow (16.7 mL/100 g per minute) and blood volume (1.84 mL/100 g) predicting progressive disease in 83.3% and 77.8% of patients, respectively. Significant changes were observed after 2, 4, and 6 months in blood flow (P < 0.031), blood volume after 4 months (P = 0.018), and mean transit time after 4 and 6 months (P = 0.030) in patients with stable disease at 6 months., Conclusions: Baseline blood flow and blood volume predicted response to therapy in our cohort.

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Background/aims: Hepatic resection in metastatic disease from colorectal cancer offers the best chance in selected cases for long-term survival. Neoadjuvant chemotherapy (NACT) has been advocated in some cases initially deemed irresectable with few reports of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of radical hepatic resection., Methodology: Between December 1995 and May 2005, 88 patients with colorectal liver metastases underwent hepatic resection with curative intent. Twenty-five of these patients, (7 males, 18 females, mean age: 58+/-9 years; range: 40-75 years) deemed as resectable cases at the time of diagnosis were treated with neoadjuvant chemotherapy. A 7-year survival analysis was performed. Chemotherapy included mainly oxaliplatin or irinotecan containing regimens for a median of 6 courses., Results: Fifteen patients (60%) had synchronous and 10 (40%) metachronous metastases. During preoperative chemotherapy tumor regression occurred in 8 cases (32%); stable disease (SD) in a further 10 patients (40%) and progressive disease (PD) developed in 7 cases (28%). The 5-year overall survival for NACT responders was 71% and only 15% for non-responders (p=0.026)., Conclusions: The response to chemotherapy is likely to be a significant prognostic factor affecting overall survival after radical hepatic resection for colorectal metastases.

Prognosis of advanced hepatocellular carcinoma is dismal when locoregional treatments have failed. Systemic chemotherapy is seldom effective in inducing objective response and prolonging survival. We report a case of complete pathological remission of hepatocellular carcinoma after three cycles of systemic chemotherapy. A 64-year-old woman presented with histologically documented hepatocellular carcinoma without associated liver disease, relapsed after earlier locoregional therapy. Surgery was not performed as thoracic computerized tomography (CT) demonstrated pulmonary bilateral nodules. The patient was treated with chemotherapy consisting of three cycles of epirubicin, cisplatin, and infusional 5-fluorouracil (ECF regimen); stable lung disease and a good partial response in the liver were obtained as documented by CT scan. Hepatic segmentectomy was therefore performed and the histologic examination revealed necrosis without evidence of residual disease. Two more cycles of adjuvant chemotherapy were infused after surgery. At 1-year follow-up the patient is alive and free of disease according to a positron emission tomography/CT scan. It is suggested that an aggressive regimen like ECF should be considered in fit patients who are not affected by concomitant liver disease.

Background/aims: The major complication for liver resection is hemorrhage. Energy sources other than electrosurgery have become popular with the promise of quick and effective vascular control. This study evaluates alternative energy sources in sealing ductal structures for use in liver resection with minimal blood loss., Methodology: Between June 1994 and December 2003, a consecutive 116 patients (59 male; 57 female; mean age: 60 +/- 11 years; range: 27-79 years) underwent surgery for primary (n = 30), metastatic liver cancer (n = 79), or benign lesions (n = 7). The extent of hepatic parenchymal division is marked on the surface with a diathermy-scored line. The arteries, veins, and bile ducts crossing the line of division are grasped, singly or in groups, by the Ligasure (Autosuture, United States Surgical Corp., Norwalk, CT) electrocautery device., Results: Fifty-eight formal hepatic resections, and 58 non-anatomical wedge resection were performed. The blood loss ranged from 100 mL to 3000 mL (median: 430 mL). Only 32 patients received preoperative blood transfusions. Perioperative mortality was nil (within 30 days following surgery), and postoperative major complications were seen in 14 patients (12%)., Conclusions: The Ligasure device uses bipolar electrothermal energy to coagulate the opposing walls of the target vessels. A feedback-control mechanism ensures that tissues are not charred by overcoagulation. This results in a high-burst strength vessel seal. Sealing is effective in vessels up to 7mm in diameter. Larger vessels require formal suture or stapling. This described technique is simple, rapid, safe for parenchymal division during hepatectomy, resulting in minimal blood loss.

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

Background/aims: Various percentages of iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy have been reported in the literature. The aim of this study was to analyze a homogeneous cohort of patients in order to evaluate the evolution and management of this complication., Methodology: We retrospectively reviewed the clinical charts of 80 patients with primary or metastatic liver tumors who received 186 hepatic arterial infusion chemotherapy courses of 5-fluorouracil, cisplatin and mitomycin-C. All of the patients complaining of upper gastrointestinal symptoms during or after hepatic arterial infusion underwent esophagogastroduodenoscopy., Results: Esophagogastroduodenoscopy was performed in 14 patients, all of whom had gastroduodenal ulcers. Two of ten investigated patients were Helicobacter pylori positive. All of the patients were treated with a proton pump inhibitor and five also received major analgesics. All of the ulcers healed without complications. Six patients did not continue with hepatic arterial infusion for reasons other than ulcers. Eight patients received a subsequent hepatic intra-arterial chemotherapy course, five despite the persistence of an active ulcer., Conclusions: Iatrogenic gastroduodenal ulcers are probably due to ischemia and the direct toxicity of the anticancer agents. They are Helicobacter pylori independent and do not represent an absolute contraindication for the continuation of hepatic intra-arterial chemotherapy.

Aims and Background: We previously reported encouraging response rates and survival with combined intra-arterial (i.a.) chemotherapy and chemoembolization in unresectable hepatocellular carcinoma. We therefore evaluated a new program combining three courses of i.a. chemotherapy with chemoembolization administered every 28 days., Patients and Methods: The treatment regimen consisted of L-leucovorin (100 mg/m2 i.v.), fluorouracil (800 mg/m2 i.a.), and carboplatin (250 mg/m2 i.a.). Chemoembolization with mitoxantrone (10 mg/m2) plus ethiodized oil and gelatin sponge was performed immediately after. The same treatment was given every 28 days for 3 times., Results: Twenty-eight patients entered the study and were assessable for response and side effects. There were 24 males and 4 females (median age, 68 yrs; range, 42-75). TNM stage was II-III in 20 and IVA in 8; 17 were Child's A and 11 Child's B. Baseline alpha-fetoprotein was elevated in 15, and there was cirrhosis in 23. Twelve patients had a partial response (43%; 95% confidence interval, 24-63%), 13 had stabilization, and 3 progressive disease. Median survival was 16.6 months (range, 2-24). Sixteen patients had grade I-II pain and 14 grade I-II fever., Conclusions: Our results indicate that the regimen is safe and well tolerated. Despite 43% objective remissions, our results do not seem better than those obtained with less intensive regimens.

Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.