Hepatic Relapse Research Articles

Hepatic Metastasectomy in Pediatric Patients: An Observational Study

BackgroundThe role of hepatectomy for metastatic disease in children is controversial. Rationales include potential cure, obtaining a diagnosis, and guiding chemotherapy decisions. This study examines the safety and utility of hepatic metastasectomy for children at a single institution. MethodsAfter IRB approval (#22–1258), medical records were reviewed from 1995 to 2022 for children undergoing hepatic metastasectomy. En-bloc hepatectomies during primary tumor resection were excluded. ResultsHepatic metastasectomy was performed in 16 patients for a variety of histologies. Median patient age was 12.2 years [IQR 6.9–22.6], and 13/16 patients were female (81 %). Number of hepatic metastases ranged from 1 to 23 and involved between 1 and 8 Couinaud segments. Anatomic resections included 4 hemihepatectomies and 1 sectionectomy. All other resections were nonanatomic. 3/6 resections for germ cell tumor (GCT) revealed only mature teratoma, driving adjuvant therapy decisions. When indicated, median time to adjuvant chemotherapy was 19 days [IQR 11–22]. No patients had Clavien-Dindo Class III or higher perioperative morbidity. Three patients (1 GCT, 1 adrenocortical carcinoma (ACC), and 1 gastric neuroendocrine tumor (GNET) experienced hepatic relapse. The patients with relapsed GCT and GNET are alive with disease at 17 and 135 months, respectively. The patient with ACC died of disease progression and liver failure. One patient with Wilms tumor experienced extrahepatic, retroperitoneal recurrence and died. With a median follow-up of 38 months, 10-year disease-specific and disease-free survival were 77 % and 61 %, respectively. ConclusionsHepatic metastasectomy can be accomplished safely in children, may guide adjuvant therapy decisions, and is associated with long-term survival in selected patients. Level of EvidenceLevel IV. Type of StudyTreatment Study, Case series with no comparison group.

Optimization of surgical tactics in hepatic echinococcosis

Aim. Optimization of the surgical tactics in hepatic echinococcosis.Material and methods. From 2009 to 2021, 56 patients with hepatic echinococcosis have been operated: 6 patients underwent PAIR, 7 – open echinococcectomy, 18 – pericystectomy (“ideal echinococcectomy”) and 16 – anatomical hepatectomy (S2/3, S6/7 bisegmentectomy) or atypical resection. In 7 cases hemigepatectomy has been performed, in 2 – combined interventions have been performed for echinococcosis relapse of the abdominal cavity.Results. The duration of minor hepatic resection was shorter than pericystectomy and major hepatic resection. The smallest blood loss was noted in patients who underwent open echinococcectomy, anatomical and atypical hepatectomy. No complications after PAIR were noticed. The lowest incidence of postoperative complications, including biliary complications, was found after hepatic resection interventions. The lenths of hospital stay after hepatic resections was significantly shorter compared to ecinococcectomy and pericystectomy. The reccurence of hepatic echinococcosis relapse was detected in 4 (66.7%) patients after PAIR and 2 (28.6%) patients after ecinococcectomy.Conclusion. Organ-preserving techniques should be a priority in the surgical treatment of hepatic echinococcosis. The best results in terms of the early postoperative complications frequency in the hepatic echinococcosis treatment were demonstrated by minor hepatic resections. Open echinococcectomy should be performed only for central location of large cysts and (or) their massive contact with the liver vessels. Minimally invasive resection technologies demonstrate optimal short- and long-term results. Major hepatectomy should be performed very selectively and only in those cases when they have advantages over other methods, and their implementation does not lead to a loss of more than 20% of healthy hepatic parenchyma. The best long-term results showed pericystectomy and hepatectomy in comparison with echinococcectomy.

Prediction of hepatic metastasis and relapse: Concordance analysis among noninvasive liver fibrosis scores from colorectal cancers.

202 Background: Liver fibrosis, resulted from several liver diseases, are increasing up to 25% in population globally. It remains undetermined how much of an impact liver fibrosis have on the development of hepatic metastasis and relapse in colorectal cancer (CRC). Hence the aim of this study was to clarify the role of liver fibrosis on hepatic metastasis and relapse in CRC undergoing curative therapy. Methods: We enrolled consecutive 1652 patients with radical surgery as the discovery cohort, and the validation set enrolled 432 CRC patients with hepatic metastasis treatment. To determine the degree of liver fibrosis, the NFS, FIB4 and APRI were applied. The influence of liver fibrosis on hepatic metastasis and relapse was assessed by survival analyses. Nomograms with fibrosis score incorporated was established to identify the incremental value for individualized relapse estimation, which was then assessed with respect to calibration, discrimination, and clinical usefulness. Results: The high liver fibrosis score patients had significantly worse outcomes than low score in 5-year hepatic metastasis (22.6 vs . 8.7%) in discovery cohort, and RFS (58.2 vs. 44.1%) in validation cohort. Multivariate analysis revealed liver fibrosis score as an independent prognostic factor. The distribution analysis also demonstrated higher liver fibrosis score a powerful prognostic factor for hepatic metastasis and relapse. Incorporating the liver fibrosis score into the nomogram resulted in better performance evaluated by C-index and AUC than TNM staging system and clinicopathologic nomograms. Importantly, in validation cohort, the discriminatory capacity of the fibrosis score incorporated was superior to that of the CRS score in predicting RFS, as demonstrated by the C-index and AUC. The concordance study showed well agreement among NFS, FIB4 and APRI in predicting DFS and RFS. Among these three noninvasive liver fibrosis scores, NFS score performed the best in predicting hepatic specific DFS and RFS. Conclusions: The liver fibrosis was a powerful predictor of hepatic specific DFS and RFS in CRC. Fibrosis niche may be a favorable microenvironment for metastatic formation in the liver.

Outcomes of elderly patients with resectable liver metastases from colorectal cancer (CRLM): Single center experience.

34 Background: Half of patients with colorectal cancer develop liver metastases during the course of their disease. Surgery is the only potentially curative option for CRLM if resectable. Treatment of patients over 70 years old is challenging mainly because of comorbidities and other geriatric syndromes. Thus, we intended to report our experience with elderly patients with resectable CRLM. Methods: After approval by the Institutional Review Board (IRB), all records from a prospectively collected database at Centre Hospitalier de l’Université de Monréal (CHUM) were retrospectively analyzed. Clinicopathological characteristics, surgery and chemotherapy treatment modalities were reviewed. RFS and OS in patients ≥ 70y were calculated using the Kaplan Meier survival curve. Results: From 2010 to 2016, 101 patients older than 70 years were identified. Safety and surgical complications were previously reported. Median age was 75 years. CRLM were synchronous in 46.5% and metachronous in 53.5%. Relapse free survival (RFS) of patients ≥ 70 years was 33.7 months. Overall survival (OS) of patients ≥70 years was comparable to those of less than 65 years old (median OS: 56 vs 62 months; p = 0.15, respectively). Hepatic relapse showed worse survival when compared to extra-liver recurrence, mOS: 44 vs 33.2 vs 29.3 months for non-hepatic, hepatic only and hepatic with other sites respectively (trend p = 0.034). Although non-statistically significant, Patients with metachronous CRLM had superior mOS compared to those with synchronous disease (58.7 vs 44.7 months; p = 0.22). Conclusions: Survival Outcomes of patients with an age ≥ 70 years were comparable to those of younger patients and what is reported in literature. Age should not be a limiting factor in the management of elderly patients with resectable CRLM. Hepatic metastatectomies +/- chemotherapy should be offered with curative intents.

Prognostic factors value of germline and somatic brca in patients undergoing surgery for recurrent ovarian cancer with liver metastases

ObjectiveTo describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. MethodsPatients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. ResultsThirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease.In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). ConclusionsOur clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.

Sinosanal undifferentiated carcinoma with liver metastasis: surgical management

BackgroundSinonasal undifferentiated carcinoma (SNUC) is a rare tumor with poor prognosis and high incidence of distant metastasis, even when a good loco-regional control is achieved.CaseWe report the case of a 43-year-old female with SNUC diagnosis. Craniofacial resection with orbital exenteration and radiotherapy in tumor bed and lymph node chain was performed. After 10 months, SNUC hepatic relapse (sIII and sVIII) is diagnosed. We administered chemotherapy and then, surgical resection was carried out. After surgery, two new relapses were diagnosed, at 9 and 21 months where surgical management was performed in both cases. 56 months after SNUC diagnosis, the patient has no evidence of recurrence.DiscussionRecommended oncological clinical guidelines for distant metastases in SNUC are chemotherapy. Surgical management in oligometastatic disease in SNUC should be considered.

Recurrent hepatocellular carcinoma in liver transplant recipients: parameters affecting time to recurrence, treatment options and survival in the sorafenib era.

A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting. This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence. A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies. Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.

Minimal Hepatic Encephalopathy in Cirrhosis: How Long to Treat? Does Minimal Hepatic Encephalopathy Relapse after Treatment?

Minimal Hepatic Encephalopathy in Cirrhosis: How Long to Treat? Does Minimal Hepatic Encephalopathy Relapse after Treatment?

Adverse Effects of Intraoperative Blood Loss on Long-Term Outcomes after Curative Gastrectomy of Patients with Stage II/III Gastric Cancer

Background/Aims: Gastrectomy with systemic lymphadenectomy sometimes causes excessive bleeding even by experienced surgeons. The aim of this study was to evaluate how intraoperative estimated blood loss (EBL) affected the long-term outcomes after curative surgery of patients with stage II/III gastric cancer (GC). Methods: This study included 203 patients with stage II/III GC who did not receive perioperative blood transfusion between 1999 and 2015. The optimal cutoff and the prognostic significance of EBL were determined retrospectively. Results: The median EBL was 285 ml. Receiver operating characteristic curve analysis identified 400 ml as an optimal cutoff. Patients with EBL ≥400 ml were more likely to have hepatic relapse and worse prognosis compared to those with EBL <400 ml. EBL ≥400 ml was identified as an independent prognostic factor for mortality by multivariable analysis. When patients were subdivided according to administration of adjuvant chemotherapy, there was a significant difference between the EBL ≥400 and <400 ml groups in patients who underwent surgery alone, whereas the prognosis was similar for patients of both groups who received adjuvant chemotherapy. Conclusion: EBL serves as a useful predictor for risk stratification after curative gastrectomy in patients with stage II/III GC.

Extra-medullary gastric and hepatic relapse of acute lymphoblastic leukaemia in an adolescent: An unusual presentation

A 15-year-old girl, who had undergone haemopoietic stem ell transplant for high-risk acute lymphoblastic leukaemia (ALL) wo years earlier, presented with epigastric pain of two weeks’ uration. Examination revealed epigastric tenderness and mild epatomegaly. Full blood count and liver function tests were noral except for mild elevation of GGT levels (85 U/L). Urea breath est for Helicobacter pylori was negative. Upper gastrointestinal endoscopy, carried out in view of orsening epigastric pain, revealed multiple prominent discrete rythematous nodular lesions with a variegated surface (Fig. 1). ltrasound revealed hepatomegaly with multiple echogenic foci cattered throughout the liver parenchyma (Fig. 2) and mild hickening of the pancreas confirmed by magnetic resonance

Adenosquamous Pancreatic Cancer: 10 Years of Experience in a Center

Context Pancreatic adenosquamous carcinoma (PASC) represents 0.4-4% of the exocrine pancreatic neoplasms and has a more aggressive behavior than ductal adenocarcinoma, but its natural history is unknown. Objective To evaluate clinical presentation, preoperative investigations, surgical approach, histological features and follow up in PASC. Methods We reviewed clinical data of patients who underwent pancreatic resection for PASC in the last decade in our Department. Results From January 2002 to December 2011 we performed 211 pancreatic resections for malignant cancer of the exocrine pancreas and 4 of them were PASC (1.8%). All patients (4 M, averaging 63.7 years; range 54-76 years) had a tumor located in the pancreatic head. Symptoms of presentation were upper abdominal pain (2/4), hyperglycemia (2/4) and jaundice (1/4). CA 19-9 was high in 2/4 patients without jaundice. All patients underwent pancreatico­duodenectomy (mean tumor size 3.4 cm) and in 3/4 cases a vascular resection was performed. In 2/4 cases a preoperative pancreatic biopsy was positive for pancreatic adenocarcinoma. Follow up to December 2011 (mean follow up 21.3 months). Two patients had an intra-abdominal bleeding in the perioperative period: one died after an early reoperation and the other died of tumor progression after 14 months. Another patient died with hepatic relapse (follow up 8 months) and the last one developed an urothelial cancer but is still alive (follow up 42 months). Conclusion Surgical treatment is the only reasonable therapeutic approach for PASC, but early relapse is frequent. The role of non-operative therapies for PASC is less clear. If preoperatively known, PASC could be candidate to neoadjuvant therapy.

Liver transplantation (Ltx) in patients with nonresectable liver metastases from colorectal carcinoma.

577 Background: Liver resection is considered the only curative treatment of liver metastases (mets) from colo-rectal (CRC) tumors. Ltx is standard of care in selected patients with hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine tumors. Patients with non-resectable liver metastases (mets) from colo-rectal cancer (CRC) receiving palliative chemotherapy have a median survival of about 2 and 1 year from start of 1. and 2. line chemotherapy, respectively. Overall 5 years survival in CRC patients after start of palliative chemotherapy is about 5-10%. In this study we examined overall survival after Ltx in selected CRC patients. The primary endpoint of the study was overall survival at 2 years after Ltx Methods: Major inclusion criteria were: non-resectable liver mets, no extra hepatic disease or local relapse determined by PET/CT scan, CT- or MRI scan and colonoscopy. No mets. on frozen section biopsies at time of surgery, ECOG 0-1, at least one line of chemotherapy for metastatic disease. Postoperative immunosuppresion: mTOR inhibitor (Rapamune), mycofpenolmofetil and tapering doses of prednisolon. Quality of life questionnaire (EORTC-C30) pre Ltx, 3, 6 and 12 months post Ltx. Results: Thirteen men and 8 women with non-resectable liver only CRC liver mets received Ltx in the period of Nov 2006 to March 2011. Median age was 56 years (range 45-65 years). Thirteen patients had colon cancer and 8 patients had rectal cancer. The T-stage of the primary tumor was T2,T3 and T4 in 2, 16 and 3 patients, respectively. N status of the primary tumor was: pN0, pN1 and pN2 all 7 patients. Nine patients had received 1.line chemotherapy and 12 patients had received 2. or 3.line therapy. The median number of liver mets was 8 (range 2-40) and the median size of the largest lesion was 4.5cm (range 2.8-13cm). The patients had good, stabile or increased Global Health Score and Physical Function at all time points after Ltx. Fifteen patients with follow-up of 2 years or more or death within 2 years of Ltx had 2 years overall survival of 87%. Conclusions: Long term survival is obtained after Ltx in selected patients with non-resectable liver mets from CRC. The patients reported good quality of life and physical function after Ltx.

Real‐time detection of hepatic micrometastases from pancreatic cancer by intraoperative fluorescence imaging

Recently, a highly sensitive fluorescent imaging technique was developed for the real-time identification of hepatic tumors. The authors applied this procedure for the intraoperative detection of radiographically occult hepatic micrometastases from pancreatic cancer. Forty-nine consecutive patients with pancreatic cancer who underwent surgical intervention were examined. Preoperative clinical images had not revealed any hepatic metastases. On the day before surgery, indocyanine green was injected intravenously. During the operation, the liver was observed with a near-infrared camera system, and abnormal fluorescent foci were examined by frozen-section histology. The patients with hepatic micrometastases were judged to have unresectable disease and underwent only palliative surgery followed by systemic chemotherapy using gemcitabine. Abnormal hepatic fluorescence at least 1.5 mm in greatest dimension without any apparent tumor was observed in 13 patients. Among them, histologic examination confirmed micrometastases in 8 of 49 patients (16%). All patients with hepatic micrometastases had clinical T3 or T4 disease and high serum CA19-9 levels (P = .042). On follow-up computed tomography images that were obtained within 6 months after surgery, the patients with hepatic micrometastases manifested hepatic overt metastases (7 of 8 patients; 88%) more frequently than the patients without hepatic micrometastases (4 of 41 patients; 10%; P < .001). Regardless of histologic confirmation, the positive predictive value of abnormal fluorescence for the manifestation of hepatic relapse within 6 months was 77% (10 of 13 patients), and the negative predictive value was 97% (35 of 36 patients). Indocyanine green-fluorescent imaging can detect hepatic micrometastases of pancreatic cancer during surgery. The hepatic micrometastases seem to have an adverse clinical impact identical to that of evident distant metastases.

Recurrent hepatocellular carcinoma in liver transplant recipients: Parameters affecting time to recurrence, treatment options and survival in the sorafenib era

A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting. This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence. A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies. Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.

Patients Operated On for Initially Unresectable Colorectal Liver Metastases With Missing Metastases Experience a Favorable Long-Term Outcome

After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with "missing CRLMs." Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. After a median follow-up of 55 months (24-137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.

Liver Perfusion Chemotherapy With 5-Fluorouracil Followed by Systemic Gemcitabine Administration for Resected Pancreatic Cancer

Liver perfusion chemotherapy (LPC) for pancreatic cancer has been rarely undertaken in a postoperative adjuvant setting. We evaluated the feasibility and antitumor efficacy of LPC with 5-fluorouracil (5-FU) followed by gemcitabine treatment. This prospective study enrolled 27 patients who underwent pancreatic resection and subsequent LPC + gemcitabine treatment during a 3-year period. The liver was infused with 5-FU (125 mg/body per day per route) via both routes of hepatic artery and portal vein for more than 21 days. After that, gemcitabine (1000 mg/m) was administered biweekly. Portal vein thrombosis developed in 1 patient, but 89% patients tolerated LPC for more than 21 days with no life-threatening complication. Systemic administration of gemcitabine was accomplished in 93%; however, 1 patient died of serious capillary leak syndrome. No grade 4 toxicity was recorded, except for that patient. Median survival time and disease-free survival were 27.5 and 24.5 months, respectively. Hepatic relapse was observed in 25.9% (n = 7). Survival was in favor of paraaortic node-negative cases (n = 20) with a 2-year survival of 68.7%. Liver perfusion chemotherapy was feasible with acceptable toxicity. Systemic use of gemcitabine also seems to be safe for the most part. This adjuvant chemotherapy shows promising survival benefit and seems to be indicative to paraaortic node-negative tumors.

Phase II trial of repeated carcinoembryonic antigen (CEA) radioimmunotherapy (RAIT) with 131I-Labetuzumab post salvage resection of colorectal metastases in the liver

13572 Background: Complete resection of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC). As shown recently (Liersch et al., JCO 2005; 23:6763–70), RAIT with a single application of the humanized monoclonal anti-CEA antibody, 131I-labetuzumab, improved both the median overall survival (OS) and 5-yr survival rates significantly in patients post salvage resection of LM. The major adverse side effects (≤ grade 3 CTC) were transient myelosuppression and/or thrombocytopenia in patients receiving 40 to 60 mCi/m2 of 131I-labetuzumab. These encouraging results stimulated the current ongoing Phase-II trial to evaluate the safety of repeated RAIT at doses of 2 × 50 mCi/m2 (3 mos apart), post salvage resection of LM. Methods: At present, 13 patients (primary CRC: 8x UICC stage IV, 1× UICC stage III and 4× UICC stage II) who underwent surgery for LM of CRC (postsalvage mTMN stages: 4× mT4, 2× mT3, 6× mT2, 1× mT1) have received the first dose of 50 mCi/m2 131I-labetuzumab within 2 mos of LM surgery. Three months later, a second infusion of 50 mCi/m2 has already been given to 5 pts. In two, a dose reduction to 40 mCi/m2 was performed. At re-staging CT and PET scans) for the 2nd RAIT, in one patient pulmonary metastases were diagnosed and in another patient a re-resection of hepatic relapse was performed. Results: In the previous trial, at a median follow-up of 67 mos, the median OS from the first liver resection for 19 pts treated with single-dose RAIT was 68.0 mos and median DFS was 18.0 mos. Also, 5-year survival was achieved by 51.3% of RAIT pts independently of bilobar involvement, size and number of LM, or resection margins. In the current study with repeated RAIT, transient grade-4 myelosuppression (2 cases in combination with a myelotoxic thiamazol medication) occurred in 4/13 pts after the first dose (1× grade 4 thrombocytopenia). No cumulative toxicity was seen in 6 of 7 RAIT-re-treated patients. Complete bone marrow recovery was observed in all 6 cases within 5–12 weeks; in one pt severe neutropenia persisted to about week 16 post 2nd RAIT. As of January, 2006, patient compliance was 100%. Conclusion: RAIT re-treatment to-date appears to be safe, feasible, and well accepted. Extended follow-up data are being collected. [Table: see text]

Repeated hepatic resection for recurrent metastases from colorectal cancer.

Since 1980 120 patients with hepatic metastases from colorectal cancer underwent surgery at the Istituto Nazionale Tumori of Milan. Of these, 34 developed recurrence in the liver only and 11 underwent repeat surgery. The median interval between the two resections was 10 months and operative morbidity and mortality rates were 40 per cent and 9 per cent respectively. Nine patients with adequate follow-up were evaluated and after a median follow-up of 17 months four were alive and disease-free, two were alive with lung metastases and hepatic relapse and three had died. The overall median survival of these patients was 23 months.

Hepatic intra-arterial chemotherapy in anthracyclin-taxane- and vinorelbine-pretreated breast cancer patients

841 Background: Metastatic breast cancer is a challenge for medical oncologists and the mean survival after the neoplasm systemic diffusion is around 2 years. After the bone, the liver is the second metastatic site, and the hepatic relapse after 1–2 lines of chemotherapy is generally an incurable disease. Hepatic intra-arterial chemotherapy is a historical assessed procedure in colon-rectal liver mts, and recently Japanese experiences enlarged the regional application to mammary hepatic metastases with an interesting overall responses and a possible survival improvement. In the last 9 years, in our center we are applying a percutaneous implantation of hepatic arterial Port-a-Cath for secondary and primitive liver cancers, and recently we have extended these procedure to the non colon-rectal liver mts. Methods: From 2000 to 2002 we implanted our percutaneous arterial Port-a-Cath in 20 patients affected by more than 5 breast hepatic mts as the only site of disease diffusion. All the patients were pretreated with 2–3 lines of Anthraciclynes, Taxanes and Vinorelbine schedules. Median age 58 y., median ECOG PS 1, previous chemotherapic lines: 2 lines 55%- 3 lines 45%. Intra-arterial schedula infused: Cisplatin 8–10 mg/m2 x 2 /d d 1–> 3, Mitomycin-C 2 mg/m2 x 2/d d 1–> 3, 5-FU 1 gr/m2/c.i. x 72 hours, every 4–6 weeks for 6–8 courses (median interval = 5 weeks; median given courses = 6). Number of mts > 5 25%, 6 to 10 55%, > 10 20%. Results: We observed: CR 15% (12 +, 18+, 24 months), PR 40% (median 6 months), SD 20%, median progression free survival 8.5 months, median survival 13 months. Catheter related side effects: gastric-duodenal ulcer 15%, catheter displacement 10% (repositioned). Main systemic side effects (WHO score): PTL G3 10%, WBC G4 10%. Conclusions: Regional intra-arterial hepatic chemotherapy seems to be a possible option for heavily pretreated breast liver mts for the number of objective responses, for the interesting survival and for the local and systemic safety of the intra-arterial schedula proposed. The percutanous mini-invasive approach allows a safe application of the regional treatment. No significant financial relationships to disclose.

3. Parotid carcinoma after autologous bone marrow transplantation for relapsed nephroblastoma

Wilms’ tumour (WT) is the most common primary genitourinary tumour of childhood with the annual incidence of approximately 8 per million children younger than 15 years of age. Genetic plays an important role in this cancer. WT1 located on chromosome 11p13, WT2 on 11p15, loci at 1p, 7p, 16q, 17p (the p53 tumor suppressor gene), and 19q (the putative familial WT gene FWT2) are believed to harbor genes involved in the biology of WT. The majority of these children are surviving into adult life and due to the combination of genetic susceptibility, irradiation and antineoplastic treatment, are at increased risk for second malignant neoplasms (SMNs). We report the case of a young man with a parotid carcinoma occurring thirteen years after diagnosis of WT. The patient was initially treated according to the SIOP 6 Nephroblastoma protocol, comprising a 4-week two-drug (Actinomycin D, Vincristine) presurgical treatment, nephrectomy and 22-week treatment with biweekly Actinomycin D and Vincristine. No radiation therapy was given. Nine months after the end of therapy he experienced an isolated hepatic relapse, treated with Peptichemio (450 mg/m2), two courses of Cisplatin (40 mg/m2/day for 5 days) and Etoposide (100 mg/m2/day for 5 days) and two cycles of the combination Ifosfamide (2 gr/m2/day for 5 days), Doxorubicin (40 mg/m2/day for 2 days), Vincristine (1.5 mg/m2). Resection of a complete necrotic lesion at the fourth hepatic segment was subsequently performed. Treatment was completed with high dose association of Melphalan (200 mg/M2) and Vincristine (4 mg/M2) followed by autologous bone marrow transplantation (BMT). After 13 years since WT diagnosis and 11 years after BMT the patient presented a right non tender, homogeneous and mobile parotideal mass. After the total parotidectomy the diagnosis was consistent with a low-grade mucoepidermoidal carcinoma. In the National WT Study Group review regarding 43 SMNs out of 5278 patients enrolled between 1969 and 1991 the relevant risk factor for developing a SMN were radiation therapy (RT), the association of Doxo-rubicin and RT and utilization of chemo-therapy for the treatment of the relapse. All these risk factors were present in the only reported case of parotideal carcinoma in these series. In the SIOP survey RT was related to secondary bone cancer and the use of epipodophyllotoxin with leukemia occurrence. On these basis in our patient a clear pathogenetic mechanism is lacking, then we can also attribute the secondary parotid carcinoma simply to the chance. Physician needto be aware that even unusual SMNs, can develop also in subjects that for their primary malignancy and related treatment are at low risk.