Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ² test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cohort Studies ; Colorectal Neoplasms/pathology* ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/secondary* ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastases is one of the most difficult and challenging points in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline includes the diagnosis and follow-up, prevention, MDT effect, surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, and with advanced experience, latest results, detailed content, and strong operability.
Chemotherapy, Adjuvant ; China ; Colorectal Neoplasms ; pathology ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; therapy ; Neoadjuvant Therapy ; Practice Guidelines as Topic

A 66-year-old female patient was diagnosed with hepatocellular carcinoma accompanied by neuropathic pain induced by a metastatic tumor that compromised root and spinal canal. Although her pain was relieved following medical treatment, breakthrough pain occurring 1-2 times a day was still distressing. Neuropathic pain in her right lower limb caused discomfort and irritability and decreased her quality of life. We had limited options to adjust her prescription drug regime, due to the side effect of these drugs. Although acupuncture therapy was only performed at her home once a week, the efficacy was outstanding. The patient did not report any further instances of breakthrough pain, and she did not require additional bolus morphine. She could comfortably live in her familiar surroundings with her family and did not require any emergency room visits or admission into the hospital during the last month of her life. She had excellent quality of life in the terminal period of her life, and could even participate in a family function during this time. The present case report suggests that acupuncture may have a role in treating neuropathic pain induced by bone metastasis in patients with advanced cancer across clinical and in-home settings.
Acupuncture Therapy ; Aged ; Bone Neoplasms ; complications ; secondary ; Carcinoma, Hepatocellular ; pathology ; Female ; Home Care Services ; Humans ; Liver Neoplasms ; pathology ; Neoplasms ; pathology ; Neuralgia ; etiology ; therapy ; Quality of Life

OBJECTIVE: To explore the prognostic factors of patients with unresectable liver metastasis colorectal cancer after failed conversion chemotherapy. METHODS: A retrospective, case-controlled study was performed. Study subjects were 105 patients who were diagnosed with synchronous liver metastasis colorectal cancer after failed chemotherapy (metastasis evaluated as unresectable after the conversion chemotherapy) at Xinhua Hospital, Shanghai Jiaotong University from January 2012 to December 2015. Overall survival(OS) was retrospectively analyzed using Kaplan-Meier method. Log-rank test was used to compare survival among groups. Univariate and multivariate analysis was conducted for prognosis using Cox regression model. RESULTS: Of 105 cases,70 were male and 35 were female with median age of 60 years old. Twenty-one patients had right colon cancer, 41 had left colon cancer, 42 had rectal cancer and 1 had synchronous cancers(sigmoid colon and rectum). One hundred and two (97.1%) patients were cT3-4 and 90 patients were cN+ (imaging diagnosis). Eighty-nine (84.8%) patients were loaded with 2 or more liver metastases with the median maximum diameter of 48.3 mm. The patients were followed up for 3 to 43 months from the day of diagnosis. The median OS was 11 months (interquartile range, 8-18). The median OS of patients with cN0, cN1 and cN2 stage was 17, 13 and 10 months, respectively(P=0.026). The median OS of patients with single lesion, 2-3 lesions, 4-10 lesions and more than 10 lesions was 15, 15, 17 and 9 months, respectively (P=0.002). OS of patients with maximum diameter of liver metastatic lesion ≤ 50 mm, 51-100 mm and >100 mm was 15, 10 and 8 months, respectively(P=0.003). The median OS of patients with chemotherapy response of partial response (PR), stable disease (SD) and progressive disease (PD) was 17, 14 and 8 months, respectively(P<0.001). OS was 17 months in patients receiving second line chemotherapy and was 10 months in those without second line chemotherapy (P<0.001). OS in patients undergoing primary tumor resection was 13 month and in those without primary tumor resection was 9 months; the difference was not significant (P=0.060). Multivariate analysis showed that cN2(HR=2.115, 95%CI:1.089-4.109, P=0.027), the maximum diameter of liver metastatic lesion more than 100 mm (HR=3.112, 95%CI:1.455-6.657, P=0.003), chemotherapy response of PD (HR=4.435, 95%CI:2.506-7.533,P<0.001) and without second line chemotherapy(HR=4.432,95%CI:2.186-8.986, P=0.010) were independent prognostic factors. CONCLUSIONS For patients with unresectable liver metastasis from colorectal cancer after failed conversion chemotherapy, prognostic factors include cN2, the maximum diameter of liver metastatic lesion, chemotherapy response and second line chemotherapy. Whether the resection of primary tumor can prolong OS further study.
Antineoplastic Agents ; therapeutic use ; China ; Colorectal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Failure

OBJECTIVETo investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT).

METHODFrom March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years.

RESULTSA total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%.

CONCLUSIONSOrgan preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.

Adult ; Aged ; Anal Canal ; surgery ; Biopsy ; Chemoradiotherapy ; Digestive System Surgical Procedures ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; secondary ; surgery ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; prevention & control ; Organ Preservation ; Quality of Life ; Rectal Neoplasms ; mortality ; surgery ; therapy ; Reoperation ; Salvage Therapy ; Survival Rate ; Treatment Outcome ; Watchful Waiting ; methods

Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients' demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.
Ablation Techniques ; adverse effects ; Adult ; Aged ; Aged, 80 and over ; Chemoembolization, Therapeutic ; adverse effects ; Female ; Gastrointestinal Neoplasms ; pathology ; therapy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Male ; Middle Aged ; Pulsed Radiofrequency Treatment ; adverse effects ; Survival Analysis

OBJECTIVEThe aim of this study was to analyze the clinical features and prognostic factors in patients with brain metastasis from colorectal cancer (CRC).

METHODSClinical materials of 45 colorectal cancer patients who developed brain metastasis were collected, and the data and follow-up data of those patients were retrospectively analyzed.

RESULTSMost brain metastases were from rectal cancer (64.4%), and 80.0% of the 45 cases had extracranial metastases. The most common extracranial metastatic site was the lung (57.8%), followed by the liver (35.6%). All the brain metastases in patients with liver metastases were supratentorial, while in contrast, 44.8% of the patients without liver metastasis had subtentorial metastasis, showing a significant difference between them (P<0.05). The interval time from diagnosis of CRC to the development of brain metastases in case of Dukes D stage was 12.0 months, significantly shorter than that in the cases of Dukes A stage (24.0 months), B (36.0 months) and C (29.0 months) (P<0.05). The interval time was also shorter in the patients who developed extracranial metastasis within one year than those more than one year (12.0 months vs. 38.0 months)( P<0.05). The median survival time of patients with brain metastasis from colorectal was 6.0 months, with a 1-year survival rate of 21.1% and 2-year survival rate of 3.3% only. Univariate analysis showed that the median survival of patients with a KPS score of ≥70 was 8.0 months, significantly higher than 2.0 months in those with a KPS score of <70 (P<0.05). The median survival of patients with one or two brain metastases was 8.0 months, significantly higher than 4.0 months of those with >2 brain metastases (P<0.05). The median survival time after diagnosis of brain metastasis was 4.0 months for those who received monotherapy (only steroids, only chemotherapy or only radiotherapy), significantly shorter than 10.0 months of patients who received chemoradiotherapy, and 12.0 months of those who underwent surgery (P<0.05). Comparing each two differently treated groups, the survival time of surgery combined with chemotherapy or radiotherapy group was significantly different from that of all of other groups (P<0.05). The median survival time of chemoradiotherapy group was longer than that of monotherapy, but the difference was not significant (P>0.05). Multivariate analysis showed that brain metastases >2 and treatment modality type are independent prognostic factors for survival.

CONCLUSIONSPatients initially diagnosed with a Dukes D stage primary colorectal tumor and occurrence of extracranial metastasis (especially, pulmonary metastasis) within one year are associated to an increased risk of brain metastases and have a shorter survival time. Most brain metastases in patients with liver metastases are supratentorial, while many patients without liver metastasis have subtentorial metastasis. Brain metastases >2 and the type of treatment modality are independent prognostic factors for survival. The prognosis of patients who received chemoradiotherapy is better than those treated only with chemotherapy or radiotherapy. Some subsets of patients may benefit from surgery plus chemotherapy/radiotherapy.

Brain Neoplasms ; mortality ; secondary ; therapy ; Chemoradiotherapy ; Colorectal Neoplasms ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Survival Rate ; Time Factors

Adenocarcinoma ; drug therapy ; Antibodies, Monoclonal ; adverse effects ; Drug Resistance, Neoplasm ; Female ; Fever ; chemically induced ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; drug therapy ; Middle Aged ; Quinazolines ; therapeutic use

OBJECTIVETo evaluate the application of multidisciplinary treatment (MDT) in patients with liver metastasis of colorectal cancer(CLM).

METHODSClinical data of 118 patients with liver metastasis of colorectal cancer, including 32 patients with MDT (MDT group) and 86 patients without MDT (control group), from February 2014 to April 2015 in PLA General Hospital were analyzed retrospectively. Compliance of preoperative examination and adjuvant therapy, and efficacy-associated indexes were compared between the two groups.

RESULTS(1) As compared to control group, statistically significant increase in imaging examination ratio was found in MDT group: chest CT [87.5%(28/32) vs. 40.7%(35/86), P=0.0000], abdominal MRI [84.4%(27/32) vs.61.6%(53/86), P=0.019], pelvic MRI [63.7%(7/11) vs. 24.3%(8/33), P=0.017]. The preoperative assessment of TNM staging was also higher in MDT group [100%(32/32) vs. 20.9%(18/86), P=0.0000], while there was no significant difference in accuracy rate of TNM staging between the two groups [81.3%(26/32) vs. 66.7%(12/18), P=0.2465]. (2) Rates of preoperative chemotherapy and chemotherapy completion were also higher in MDT group than those in control group [90.6%(29/32) vs. 62.8%(54/86), P=0.0033; 82.8% (24/29) vs. 57.4% (31/54), P=0.000], but conversion rate of unresectable CLM showed no significant difference [24.0% (6/25) vs. 14.3% (7/49), P=0.299 ]. (3) Rate of one-stage resection or ablation was higher in MDT group compared to control group [76.9%(10/13) vs. 36.0%(9/25), P=0.038], and resection rate of metastasis nidus was also higher in MDT group [77.0%(20/26) vs. 44.9%(13/29), P=0.015]. No significant differences were observed in rates of R0 resection, positive surgical margin, lymph node clearance, ablation of metastasis nidus, pathological complete response, postoperative chemotherapy or postoperative complications (all P>0.05).

CONCLUSIONMDT has the advantages on standardization of preoperative examination and perioperative chemotherapy, and can improve the rate of one-stage resection or ablation, as well as resection of metastasis nidus.

Aged ; Colorectal Neoplasms ; pathology ; Combined Modality Therapy ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Lymph Nodes ; Male ; Middle Aged ; Neoplasm Staging ; Postoperative Complications ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome