Recurrent Hepatic Metastases Research Articles

Survival after repeat hepatectomy for recurrent colorectal liver metastasis: A review and meta-analysis of prognostic factors

BackgroundFrequent recurrent hepatic metastasis after hepatic metastasectomy is a major obstacle in the treatment of colorectal liver metastasis (CRLM). We performed the present systematic review to evaluate the short- and long-term outcomes after repeat hepatectomy for recurrent CRLM and determine factors associated with survival in these patients. Data sourcesAn electronic search of PubMed database was undertaken to identify all relevant peer-reviewed papers published in English between January 2000 and July 2018. Hazard ratios (HR) with 95% confidence interval (95% CI) were calculated for prognostic factors of overall survival (OS). ResultsThe search yielded 34 studies comprising 3039 patients, with a median overall morbidity of 23% (range 8%–71%), mortality of 0 (range 0–6%), and 5-year OS of 42% (range 17%–73%). Pooled analysis showed that primary T3/T4 stage tumor (HR = 1.94; 95% CI: 1.04–3.63), multiple tumors (HR = 1.49; 95% CI: 1.10–2.01), largest liver lesion ≥5 cm (HR = 1.89; 95% CI: 1.11–3.23) and positive surgical margin (HR = 1.80; 95% CI: 1.09–2.97) at initial hepatectomy, and high serum level of carcinoembryonic antigen (HR = 1.87; 95% CI: 1.27–2.74), disease-free interval ≤12 months (HR = 1.34; 95% CI: 1.10–1.62), multiple tumors (HR = 1.64; 95% CI: 1.32–2.02), largest liver lesion ≥5 cm (HR = 1.85; 95% CI: 1.34–2.56), positive surgical margin (HR = 2.25; 95% CI: 1.39–3.65), presence of bilobar disease (HR = 1.62; 95% CI: 1.19–2.20), and extrahepatic metastases (HR = 1.60; 95% CI: 1.23–2.09) at repeat hepatectomy were significantly associated with poor OS. ConclusionsRepeat hepatectomy is a safe and effective therapy for recurrent CRLM. Long-term outcome is predicted mainly by factors related to repeat hepatectomy.

The metastatic microenvironment of human liver characterised by increased levels of inflammatory cytokines promotes cancer cell chemotaxis RN

Objective: Healthy human liver is immunologically equipped for effective tumour surveillance, with repertoires of potent cytotoxic lymphoid populations. Despite this, hepatic metastases are common with little known of the immune landscape that remains following hepatectomy. How the immune microenvironment of the liver responds in the presence of metastatic disease, and whether this response dictates hepatic metastatic recurrence has yet to be elucidated. We hypothesise the cytokine milieu across metastatic liver can modify the local anti-tumour response and thus influence further tumour growth. Methods: Biopsies of freshly resected tumour, tumour adjacent liver and liver at the distal resection margin (n=25) were cultured in vitro to obtain metastatic conditioned media (CM). Using an antibody array, this CM was screened for 102 cytokines, compared to CM from healthy control liver. Differentially expressed cytokines (n=12) were quantified using Luminex-based multiplex analysis. Results: IL6, CXCL1(GRO ), CXCL5(ENA 78), GCSF, GMCSF, VEGF, LIF, CCL 3(MIP-1) demonstrated significant variation in distal metastatic liver when compared to healthy donor. When analyzed by chemotaxis assay, all areas of metastatic liver induced migration of metastatic cancer cells. Furthermore, depletion of neutrophils at the distal resection margin significantly correlated with recurrent hepatic metastases. Conclusion: Healthy human liver has a highly evolved anti-tumour immune repertoire which is maintained by a complex cytokine environment. This immune landscape is perturbed in the presence of metastases, with increased expression of chemotactic cytokines and altered immune cell populations, inducing metastatic cell migration and tumour recurrence.

異時性残肝再発・肺転移切除後長期生存が得られている腫瘤形成型肝内胆管癌の1例

異時性残肝再発・肺転移切除後長期生存が得られている腫瘤形成型肝内胆管癌の1例

Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma.

A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and cells showed significantly lower OPG expression. Pyrosequencing of OPG-silenced CRC cells revealed that the OPG gene promoter was highly methylated. Treatment with demethylating agent significantly elevated OPG mRNA and protein expression. rOPG significantly decreased cell viability and MMP-2 and VEGF-A production in CRC cells. Reduced OPG immunoreactivity was associated with aggressive oncogenic behavior in CRC. Also, OPG expression was found to be an independent predictor of recurrent hepatic metastasis and independent prognostic factor for worse survival rates. We demonstrated that OPG silencing in CRC occurs through epigenetic repression, and is involved in the development and progression of CRC. Our data suggest that OPG is a novel prognostic biomarker and a new therapeutic target for the treatment of patients with CRC.

Multidisciplinary Approach to Hepatic Metastases of Intracranial Hemangiopericytoma: A Case Report and Review of the Literature.

Hemangiopericytoma is a rare primary tumor originating from Zimmerman's pericytes, with significant metastatic potential. Hepatic metastatic disease requires an aggressive approach by a multidisciplinary team of dedicated oncology specialists, to prolong survival in selected patients. We report on a patient with recurrent hepatic metastases of grade II intracranial hemangiopericytoma 5 years after initial treatment, managed by a stepwise combination of liver resection, radiofrequency ablation, and transarterial embolization. Although metastatic disease implies hematogenous dissemination, long-term survival after liver resection has been reported and major hepatectomies are justified in patients with adequate local control. Liver resections combined with transarterial embolization are highly recommended, due to hypervascularity of the tumor.

Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report)

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient’s performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

Surgical outcomes of second liver resections for recurrent hepatic metastases from colorectal cancer

To compare the clinical efficacies and safety of primary versus second liver resection for recurrent colorectal metastases to liver. Between January 2000 and March 2011, a total of 126 patients underwent liver resections for metastases from colorectal cancer at our institution. Among these, 16 patients underwent repeat liver resections. The comparisons were made for primary and second liver resections in blood loss volume, complications, hospital stay, operative duration and 1, 3, 5- year survival rates. Compared with primary liver resection group, the 1, 3, 5-year survival rates of second liver resection group were 93.8%, 56.1% and 37.4% respectively. For second hepatectomy group, blood loss volume was (323.8 ± 230.9) ml, operative duration (216.9 ± 79.7) min, postoperative hospital stay (23.4 ± 13.9) days and complication rate 18.8%. Compared with primary hepatectomy, there was no difference between two groups. Second liver resection may provide long-term survival rates similar to those of primary liver resections. Repeat liver resection is warranted when potentially curative.

Mittelfristiges, relativ tumorstabiles Outcome eines erfolgreich interdisziplinär lokal R0-resezierten, metastasierten Leiomyosarkoms der V. cava inferior mit multimodaler Behandlung

Progredient tumor-growth does not mean necessarily nihilism since (because of the latest multimodal therapeutic options) it might be possible to convert the malignant disease into a chronic stage depending on tumor entity, specific tumor-associated findings and expertise of the interdisciplinary oncological/oncosurgical team to utilize available and potential therapeutic measures. The aim of this report on an unusual case (with its patient-associated, therapeutic and prognostic aspects) of a leiomyosarcoma of the inferior vena cava with advanced tumor growth (characterized initially by pulmonary and hepatic, later on by additional vertebral metastases) is to illustrate its changeful clinical course after and during multimodal treatment episodes comprising surgical (abdomino-/vascular-/cardio- and neurosurgical-locally, R0 resection status), radiological and chemotherapeutic measures. A relatively stable disease over a specific time period of 5 years and 6 months was achieved. The 54-year old female patient with metastasized leiomyosarcoma of the inferior vena cava underwent local tumor resection en bloc with inferior vena cava segmental resection (following vascular surgical interposition of a prosthesis) and hemihepatectomy as well as resection of hepatic segment I. After recovery, a multistep and -modal treatment was initiated comprising of various protocols of systemic chemotherapy, thermoablation of recurrent hepatic metastases, various brachytherapy procedures (for hepatic and pulmonary metastases) and resection of a cerebral metastasis by a neurosurgeon including subsequent radiation. The patient demonstrates impressively that even in case of advanced tumor stage with initial, novel and recurrent metastases, a relatively stable disease over an intermediate time period (of more than 5 years) with an acceptable quality of life was achieved despite several complications.

P-0273 Hepatic Metastasis and Reccurence of Colorectal Cancer Assesment by 18FDG PET/CT

ABSTRACT Introduction Liver is the most frequent long distance metastasis site of digestive cancer. Early and accurate detection of hepatic metastasis as well as of tumoral recurrence is an important objective, especially in colorectal cancer, due to the improved 5 year surveillance rates after metastasectomy compared to nonsurgical therapy. Aim: to assess the use of 18FDG PET/CT (18 fluorodeoxyglucose positron emission tomography and computed tomography) in the detection of hepatic metastasis and recurrence of colorectal cancer. Methods Our study took place in the Emergency Clinical County Hospital (Oradea, Romania) in collaboration with PET POZITRON Diagnostic Center (Oradea, Romania). We studied 48 patients (38 men and 10 women, aged 48-74 years) who were previously treated by surgery for colorectal cancer. The FDG-PET/CT examination was made with the Siemens Biograph 16 unit (Germany) at 1 hour after the automatic infusion of FDG, at doses previously adjusted to individual parameters of each patient. Afterwards the recurrence and/or metastasis diagnosis was confirmed by colonoscopy, histology or other imaging techniques. At the same time, CEA (carcinoembryonic antigen) was measured. The statistical analysis was made with the help of SPSS application (Statistical Package for the Social Sciences). Results The time interval between the surgical intervention and PET/CT evaluation varied between 6 months to 8 years, with a mean value of 2.6 years. Out of the 48 studied patients recurrence and/or metastasis were diagnosed in 36 (75%) patients, including 8(16.7%) recurrences, 26 (54.2%) metastasis and 2 (4.1%) recurrence with metastasis. The diagnosis sensibility of identifying recurrent colorectal cancer and hepatic metastasis was 93% and its specificity was 84%. Treatment plans were changed in 8 (16.7%) patients after PET/CT evaluation. Localised metastasis were detected in the liver and lungs of 2 (4.2%) patients who were referred to surgery instead of chemotherapy. 4 patients (8.3%) had disseminated metastasis and were referred to chemotherapy. 2 (4.2%) patients with high levels of CEA and indication of iv chemotherapy in which conventional imaging showed no lesions, had at PET/CT evaluation, the following aspects: 1 patient had a recurrence and was resent to surgery and the other one, had lung and bone metastasis being thus referred to radio and chemotherapy. In our study group besides hepatic metastasis we also found metastasis in: lung (9/36, 25%), abdominal cavity and mesentery (8/36, 22%), retroperitoneal (7/36, 19%). Other secondary localizations included bone, lymph nodes, peritoneum and brain but the preferred metastasis foci were liver and lung. In some patients, beside conventional imaging examinations, PET/CT offered restaging of the disease. Conclusion 18FDG PET/CT examination can detect with high sensibility and specificity tumoral recurrences and/or hepatic metastasis. At the same time, in patients with surgically treated colorectal cancer it can identify lesions with abnormal metabolic levels, incipient occult metastasis and can orientate therapeutic measures.

Heme products post-radiofrequency ablation obscure tumor recurrence on MR but not on PET-CT.

A 76-year-old male with non-small-cell lung cancer, post lobectomy, presented with hepatic metastatic disease and underwent radiofrequency ablation (RFA), a minimally invasive and safe approach for treatment of liver tumors [1]. Gadolinium-enhanced MRI of the patient performed at our institution 5 months post-RFA reported increased T1 signal at the RFA site believed to be post-RFA blood products (Fig. 1). RFA leads to palliation, increased survival, and is better tolerated than other ablative techniques. It has also been associated with a low rate of local recurrence [2]. Post-RFA, the target lesion typically has hyperintense signal with T1-weighting, low signal on T2-weighting, and is non-enhancing following post-gadolinium administration. Recurrent disease typically demonstrates new enhancement, increased size, and development of T1-weighted hypointense and T2-weighted hyperintense regions [3–5]. Fig. 1 Gadolinium-enhanced MRI of a 76-year-old male with non-small-cell lung cancer who presented with hepatic metastatic disease and underwent radiofrequency ablation (RFA). Arrows indicate what is believed to be post-RFA blood products Subsequent positron emission tomography/computerized tomography (PET/CT) of the patient demonstrated focal FDG uptake on the corresponding sagittal image, at the border of the prior RFA ablation zone, with maximal SUV of 6.9, characteristic for recurrent hepatic metastasis (Fig. 2). The photopenic area was at the epicenter of the RFA site. PET/CT imaging is also used to monitor residual tumor or recurrence after RFA. Lesions that show increased 18-fluorodeoxyglucose (FDG) uptake on PET become photopenic immediately after RFA, suggestive of complete ablation. Focal areas of increased FDG uptake within the ablated zone are suspicious for residual or recurrent disease. Reactive tissue is typically present in the periphery of the ablated lesion and has uniform low-grade FDG uptake, unlike the focal nodular intense uptake observed with active tumor [6–10]. Fig. 2 a–c Positron emission tomography/computerized tomography (PET/CT) demonstrates focal FDG uptake on the sagittal image. The photopenic area (arrowheads) is at the epicenter of the RFA site PET/MRI fusion (Fig. 3) completed on a dedicated MimVista 5.2 (Cleveland, OH) workstation illustrates the area of FDG uptake, representing the recurrent tumor, to be at the edge of the intense T1 signal abnormality and which actually corresponded to subtle gadolinium enhancement that was difficult to differentiate from adjacent post-RFA blood products on T1 signal on MR. Subtle T1 post-gadolinium enhancement adjacent to already intense T1 signal from blood products may be overlooked on MRI but more readily detected as an FDG-avid lesion on PET. PET/CT is superior to anatomic imaging in the surveillance of patients treated with RFA for malignant hepatic tumors and is more cost-effective [8, 11]. Lesions that on CT or MR have no enhancement or diffuse peripheral enhancement may often have focal uptake on PET/CT. This added information can be used to direct biopsy or repeat RFA [12]. Fig. 3 PET/MRI fusion illustrates the area of FDG uptake (arrows), representing the recurrent tumor, to be at the edge of the intense T1 signal abnormality (arrowheads) Patient underwent surgical resection of liver segment VI. Pathology report demonstrated sheets and cords of poorly differentiated cells displaying pleomorphism and hypochromasia with a high nuclear-cytoplasmic ratio, prominent nucleoli, and frequent mitoses. The uninvolved liver showed centrilobular congestion. Fig. 4 Pathology results showed sheets and cords of poorly differentiated cells displaying pleomorphism and hypochromasia with a high nuclear-cytoplasmic ratio, prominent nucleoli, and frequent mitoses. The uninvolved liver showed centrilobular congestion ( ...

Radiofrequency Ablation for Metachronous Hepatic Metastases From Gastric Cancer

The objective of this study was to evaluate the results of radiofrequency ablation (RFA) for the treatment of metachronous hepatic metastases from gastric adenocarcinoma. Between January 2000 and February 2008, we retrospectively reviewed 7 cases for which RFA was performed for treating metachronous hepatic metastases after resection of the primary gastric adenocarcinoma. The median period between curative gastrectomy and metachronous hepatic metastasis was 14 months (range: 6 to 48 mo). The median survival of the patients was 11.0 months (range: 5.5 to 39.2) after the first detection of hepatic metastases and 10.0 months (range: 5 to 38.2) after the first RFA. Hepatic metastases recurred 3 to 21 months after RFA in all patients. A second RFA was performed for a single recurrent hepatic metastasis in 1 patient and this patient survived more than 3 years without recurrence until the time of this study. In conclusion, the efficacy of RFA alone for metachronous hepatic metastases from gastric adenocarcinoma was disappointing due to multiple intrahepatic recurrences. Combination therapy such as systemic chemotherapy or hepatic arterial infusion chemotherapy adjuvant to RFA would more reasonable for treating hepatic metastases from gastric cancer.

Prognostic Factors for Survival in Patients with Hepatic Recurrence After Curative Resection of Gastric Cancer

This study was done to evaluate the prognostic factors that may affect the survival of patients with recurrent hepatic metastasis after curative resection of gastric cancer. We reviewed the medical records of 73 patients with recurrent hepatic metastasis after surgical treatment of gastric cancer from January 1995 to December 2005. Prognostic factors were classified into three groups: primary tumor factors, recurrent hepatic factors, and treatment factors. The prognostic values of these factors were assessed using univariate and multivariate analyses by the log-rank test in the Kaplan-Meier method and Cox's proportional hazard model. The overall median survival rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4-24.6 months]. The median survival rate after diagnosis of recurrent hepatic metastasis was 5 months (95% CI 3.5-6.5 months). Univariate analysis showed that the favorable prognostic factors were stage I and II among the primary tumor factors, no extrahepatic metastasis and unilobar distribution among the recurrent hepatic factors, and radiofrequency ablation (RFA) +/- chemotherapy among the treatment factors when operative treatment had been excluded. The independent favorable prognostic factors revealed by the multivariate analysis were no extrahepatic metastasis and RFA +/- chemotherapy. The median survival rate of patients who had two favorable prognostic factors was 27 months (95% CI 0-66.38 months). Improvement in the survival rate can be expected with RFA +/- chemotherapy for patients with recurrent gastric cancer in the liver without extrahepatic metastasis.

Extension of hepatic necrosis secondary to current arcing to surgical clips: a potential complication of radiofrequency ablation

The authors present a case report of a 67-year-old woman who underwent radiofrequency ablation of recurrent hepatic metastases. She was managed 2 years previously with a right hemi-hepatectomy. Subsequent to RF ablation she developed hepatic necrosis extending in a linear fashion to two of the metallic surgical clips at the free edge of the liver, consistent with current arcing.

Induced fluorescence of breast cancer in the mouse model: A simple technology to improve visualization of malignant tissue during breast cancer surgery

10557 Background: Accurate identification of all malignant tissue at the time of lumpectomy or mastectomy can at times be challenging. When positive margins are discovered, significant additional time and effort may be required by the surgeon to complete the initial procedure. Inducing the cancer cells to be fluorescent offers the potential to improve the surgeon’s ability to rapidly and accurately identify and excise the malignant tissue at the time of surgery. We have previously demonstrated the feasibility of inducing tumor fluorescence with fluorophore-tagged anti-tumor antigen antibodies using a human colon cancer cell line. We present here our recent results using a human breast cancer cell line in the nude mouse. Methods: A human breast cancer cell line, MDA-MB-468 known to express CA 15–3 was used. Breast cancer cells were subcutaneously implanted in 14 nude mice. Three to five weeks after injection, tumor nodules were easily visible and palpable. Using the tail vein method, mice were injected with fluorophore-tagged anti-CA 15–3 and were examined using a small animal imaging system with a 470 nm light source. Mice were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band-pass filter and were observed through filtered goggles. Results: Tumor nodules could be seen to fluoresce through the skin when illuminated with a 470 nm light source. When tumor nodules were exposed and examined with white light, the nodules could be seen but when illuminated with the 470 nm light source, tumor fluorescence allowed clear identification of nearby small tumor nodules and clear identification of tumor margins easily distinguishable from the normal tissue. Conclusions: For this technology to work, tumor antigens must be known and antibodies to these antigens available. It is easy to perform, requires no complex equipment or operator expertise and could be easily adapted to surgical oncology in any hospital setting. It has the potential to improve surgical accuracy in women undergoing initial lumpectomy or mastectomy as well as axillary lymph node dissection or sentinel node biopsy. In addition it could aid in the surgery of patients undergoing resection of isolated recurrent hepatic or pulmonary metastases. No significant financial relationships to disclose.

A CASE OF REHEPATECTOMY FOR A RECURRENT HEPATIC METASTASIS WITH ADJACENCY TO THE REMNANT MAIN GLISSON'S SHEATH

We herein report a case of rehepatectomy for a recurrent hepatic metastasis with adjacency to the remnant main Glisson's sheath. The patient was a 61-year-old man who underwent a high anterior resection (D2) and an insertion of an intra-hepatic arterial catheter for a rectal carcinoma with hepatic metastases in June, 1994. Miocroscopic findings showed moderately differentiated of ss, n 1 (+), P0, H2, ly1, v0, aw (-), ow (-), ew (-), and in stage IV. adenocarcinoma. Intra-hepatic arterial infusion chemotherapy was performed after the surgery. Extended left lobectomy and a S 7 partial resection were performed about 8 months after the initial surgery. Single hepatic metastatic lesion was detected about 20 months after the initial hepatectomy. Abdominal CT revealed a 7-cm sized hepatic tumor invaded the remnant main Glisson's sheath that suggested a difficulty in resecting it. But we successfully performed rehepatectomy curatively. The postoperative course was uneventful. There have been no signs of recurrence for one year after the rehepatectomy.

Comparison by carcinoembryonic antigen doubling time of hepatic injection and infusion for unresectable hepatic metastasis from colorectal cancer

This study explored the efficacy of hepatic arterial therapy, comparing both injection and infusion of 5-fluorouracil (5-FU) in prolonging the survival of 92 patients with recurrent unresectable hepatic metastasis from colorectal cancer. With respect to pretreatment carcinoembryonic antigen doubling time (CEA-DT), 56 patients were treated with intra-arterial injection, and 36 with intra-arterial infusion. In 21 patients with a CEA-DT of less than 40 days, the cumulative survival of patients treated with arterial injection was significantly longer than that of patients treated with arterial infusion. In 45 patients with a CEA-DT of 40-80 days, the survival curves of patients did not differ from each other. Of the remaining 26 patients with a CEA-DT of more than 80 days, those treated using arterial infusion had an excellent prognosis, in contrast to those treated using arterial injection, with statistical significance. CEA-DT may be useful when choosing a chemotherapy regimen, and may help to accurately establish the prognosis of patients with unresectable hepatic metastasis from colorectal cancer.

CT arterial portography for detecting recurrent hepatic metastases.

CT arterial portography for detecting recurrent hepatic metastases.