Colorectal cancer and dormant metastases:Put to sleep or destroy?

After reading the review by An et al“Biological factors driving colorectal cancer metastasis”,which covers the problem of the metastasis of colorectal cancer(CRC),I had a desire to discuss with readers one of the exciting problems associated with dormant metastases.Most deaths from CRCs are caused by metastases,which can be detected both at diagnosis of the primary tumor and several years or even decades after treatment.This is because tumor cells that enter the bloodstream can be destroyed by the immune system,cause metastatic growth,or remain dormant for a long time.Dormant tumor cells may not manifest themselves throughout a person’s life or,after some time and under appropriate conditions,may give rise to the growth of metastases.In this editorial,we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation,as well as factors that contribute to the activation of dormant metastases in CRCs.We will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases

BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases

BACKGROUND Evaluating the psychological resilience of lung cancer(LC)patients helps understand their mental state and guides future treatment.However,there is limited research on the psychological resilience of LC patients with bone me-tastases.AIM To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience.METHODS LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University.The psychological scores of the enrolled patients were collected.They were then grouped based on the mean psychological score:Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group.The baseline data(age,gender,education level,marital status,residence,monthly income,and religious beliefs),along with self-efficacy and medical coping mode scores,were compared.RESULTS This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023,with an average psychological resilience score of 63.24±9.96 points.After grouping,the low-score group consisted of 69 patients,including 42 males and 27 females,with an average age of 67.38±9.55 years.The high-score group consisted of 73 patients,including 49 males and 24 females,with a mean age of 61.97±5.00 years.χ2 analysis revealed significant differences between the two groups in education level(χ2=6.604,P=0.037),residence(χ2=12.950,P=0.002),monthly income(χ2=9.375,P=0.009),and medical coping modes(χ2=19.150,P=0.000).Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores(t=3.383,P=0.001)and lower age than the low-score group(t=4.256,P<0.001).Furthermore,multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience[odds ratio(OR)=0.926,P=0.035,95%confidence interval(CI):0.862-0.995],while age(OR=1.099,P=0.003,95%CI:1.034-1.169)and medical coping modes(avoidance vs confrontation:OR=3.767,P=0.012,95%CI:1.342-10.570;resignation vs confrontation:OR=5.687,P=0.001,95%CI:1.974-16.385)were identified as independent risk factors.A predictive model based on self-efficacy,age,and medical coping modes was developed.The receiver operating characteristic analysis showed an area under the curve value of 0.778(95%CI:0.701-0.856,P<0.001),indicating that the model has good predictive performance.CONCLUSION LC patients with bone metastases are less psychologically resilient than the general population.Factors such as self-efficacy,age,and medical coping modes influence their psychological resilience.Patients with low self-efficacy,old age,and avoidance/resignation coping modes should be closely observed.

Feasibility and limitations of combined treatment for lateral pelvic lymph node metastases in rectal cancer

Colorectal cancer ranks among the most commonly diagnosed cancers globally,and is associated with a high rate of pelvic recurrence after surgery.In efforts to mitigate recurrence,pelvic lymph node dissection(PLND)is commonly advocated as an adjunct to radical surgery.Neoadjuvant chemoradiotherapy(NACRT)is a therapeutic approach employed in managing locally advanced rectal cancer,and has been found to increase the survival rates.Chua et al have proposed a combination of NACRT with selective PLND for addressing lateral pelvic lymph node metastases in rectal cancer patients,with the aim of reducing recurrence and improving survival outcomes.Nevertheless,certain studies have indicated that the addition of PLND to NACRT and total mesorectal excision did not yield a significant reduction in local recurrence rates or improvement in survival.Consequently,meticulous patient selection and perioperative chemotherapy may prove indispensable in ensuring the efficacy of PLND.

Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

Effect of magnetic resonance imaging in liver metastases

This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving prognosis.This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Current status of nerve infiltration by skip metastases in colorectal cancer

Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence rate of 24.07 per 10million,and 286,200 deaths.China accounts for approximately 30%of new cases and deaths from CRC worldwide,with East Asia accounting for over 75%.Initially,CRC presents as local tumor growth,but it has the potential to spread to other body parts over time.Perineural infiltration(PNI)is a relatively less discussed route of diffusion,yet it plays a crucial role in the progression and prognosis of CRC.PNI often occurs alongside local lymph nodes and distant metastases,posing challenges for treatment and management.Clinical symptoms,radiographic findings,and histopathological examination can be used to diagnose PNI with skipmetastasis.Symptoms commonly include local pain,paresthesia,andmotor impairment.Imaging helps identify the mass’s location and relationship to nerves,whereas histopathological examination confirms the diagnosis.Treatment of PNI skipmetastases is similar to other CRC metastases,including surgical resection,chemotherapy,radiotherapy,and targeted therapy.Surgical resection is the primary therapeutic approach,but the wider range of metastasis in PNI skip transfer may limit its feasibility.In cases where surgical resection is not possible,chemotherapy,radiotherapy,and targeted therapy are used to control tumor metastasis.In conclusion,PNI skip metastases increase the risk of poor prognosis for CRC,requiring a comprehensive approach with multiple treatments to prevent disease progression.Early detection and treatment are vital to improving prognosis.

Planning Target Volume Margin in Linac-Based Stereotactic Radiosurgery for Brain Metastases

Background: The treatment of brain metastases with radiotherapy has shifted to the use of Stereotactic Radio-surgery (SRS). The technical issue of expanding the treatment volume around the Gross Tumor Volume (GTV) is a current debate. Radiotherapy centers use variable GTV-PTV margins, ranging from one to 2 mm. Material and Methods: We performed a dosimetric comparison in plans of twenty patients using three margins: PTV zero, PTV1, and PTV2. We also developed imaginary Peel volumes. These volumes are described as follows: Peel1 = PTV1 − GTV, Peel2 = PTV2 − GTV. Results: Our results showed that the mean PTV volume differed significantly across the different margins (p = 0.000). The V12 of the brain significantly varied as a function of PTV margin (p = 0.000). The target coverage and plan quality indices were not significantly different. The Peel volume dosimetric analysis showed that the mean dose was significantly higher in the nearby normal brain tissue: Peel1 (p = 0.022) and Peel 2 (p = 0.013). Conclusion: According to our dosimetric analysis, expanding the GTV into a PTV by 1 mm margin is more convenient than 2 mm.

Current Epidemiology of Intracranial Metastases in Two University Teaching Reference Hospitals of the Town of Yaounde, Cameroon: Analysis of 35 Cases Recorded in the Neurosurgery Departments

Background: The incidence of intracranial metastases (ICMET) has been steadily rising, and its frequency with respect to primary brain tumours is relatively high. Objective: The objectives of this study were to elucidate the current epidemiology and describe the clinical, diagnostic and therapeutic features of ICMET in Yaounde. Method and findings: A descriptive cross-sectional study was done in the neurosurgery departments of the General and Central Hospitals of Yaounde during the period from January 2016 to December 2022. We included all medical booklets of patients admitted for a tumoral intracranial expansive process with our target population being patients with histological evidence of ICMET, and did a retrospective inclusion of data using a pre-established technical form aimed at collecting sociodemographic data, clinical data, paraclinical data, and the treatment procedures. Analysis was done using the SPSS statistical software. A total of 614 cases of intracranial tumors were included among whom 35 presented histological evidence of ICMET. This gives a frequency of 5.7%. The sex ratio was 0.94, the mean age was 55.68 +/- 14.4 years, extremes 28 and 86 years and the age range 50 - 59 was affected in 28.57% of cases. The clinical presentation included signs of raised intracranial pressure (headache, blurred vision, vomiting) in 26 cases (74.3%), motor deficit 48.6%, seizures 17.1%. The mode of onset was metachronous in 71.4% and synchronous in 28.6%. The imaging techniques were cerebral CT scan in 82.9%, cerebral MRI in 40%, TAP scan in 22.9%. The metastatic lesions were supratentorial in 94.3% and single in 62.9%. The primary cancers found were breast cancer (31.4%), lung cancer (25.7%), prostate cancer (17.1%), thyroid cancer (5.7%), colon cancer (2.9%), and melanoma (2.9%). The therapeutic modalities were total resection (68.6%), radiotherapy (37.1%). Conclusion: Intracranial metastases are relatively frequent. There is a female sex predominance and the age group 50 - 59 years is the most affected. Brain metastases mostly occur in patients with a history of known primary tumor. The clinical signs mainly include signs of raised intracranial pressure, motor deficit, seizures and mental confusion. Cerebral CT Scan is the main imaging technique used. Most of the lesions are single and supratentorially located. The primary cancers most represented include breast cancer, lung cancer and prostate cancer. Surgery is the main treatment procedure. The adjuvant treatment (radiotherapy, chemotherapy) was limited.

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis

To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database.METHODSSEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved.RESULTSA total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival.CONCLUSIONPancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

An Analysis of Prospective Outcome of Re-resection for Recurrent Live Cancer and Extrahepatic Metastases,a Follow-up of 267\Cass

Objective To evaluate the prospective outcome and summarize experience in re-resection for recurrent liver cancer and extrahepatic metastases. Methods The clinical data of 267 patients with recurrent primary liver cancer (PLC) after re-resection from January 1960 to July 2000 were retrospectively analyzed. Re-hepatectomy was performed on 205 cases, resection of extrahepatic metastases on 51 cases and combined resection of recurrent liver cancer and extrahepatic metastases on 11 cases. The clinico-pathologic features, operation type and survival were compared. Results The types of liver re-resection included left lateral lobectomy in 11.2% of patients, hemihepatetomy and extended hemi-hepatectomy in 4.4%, local radical resection in 68.3%, other subsegmentectomy in 17.1%. The peak recurrence rate (64.4%) occurred at 1–2 years. The overall 1-, 3, 5- and 10-year survival rates after second resection were 81.0%, 40.3%, 19.4% and 9.0% respectively, while they were 77.5%, 29.8%, 13.2% and 6.61% respectively after the third resection. The median survival time was 44 months. The re-resection with extrahepatic metastases also provided the possibility of longer survival. Conclusion The results suggest that subsegmentectomy and local excision is appropriate for the hepatic repeat resection. The peak recurrence may be correlated with portal thrombus and operative factor. The re-resection can be indicated not only in intrahepatic recurrent metastases but also in extrahepatic metastases in selected patients. Re-resection has become the treatment of choice for recurrence of PLC, as neither chemotherapy nor other nonsurgical therapies can achieve such favorable results. Key words prospective outcome - re-resection - primary liver cancer - recurrence - extrahepatic metastases

Successful Surgical Treatment of Metachronous Oligometastases from Non-B, Non-C Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) rarely metastasizes to bone or mediastinum. In some patients, surgical treatment of oligometastatic lesions from colorectal cancer, breast cancer, or non-small cell lung cancer results in satisfactory survival. However, data concerning oligometastatic lesions from HCC are scarce. We report the case of a patient with long-term survival after resection of metachronous oligometastases of HCC. A 54-year-old woman underwent hepatic resection for non-B, non-C HCC. A solitary left tenth rib tumor was detected 20 months after initial surgery and was surgically resected. A solitary mediastinal tumor was detected 6 months after the second operation and the patient again underwent surgical resection. Histopathological examination of both lesions confirmed metastasis of HCC. The patient has had no further recurrence 7 years after initial surgery without chemotherapy or radiotherapy.

Colorectal cancer with liver metastases:Neoadjuvant chemotherapy,surgical resection first or palliation alone?

Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for &#x0003e; 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.

Role of surgery in colorectal liver metastases:Too early or too late?

As colorectal cancer and colorectal liver metastases become a serious public health problem,new treatment modalities are needed in order to achieve better results. In the last decade there has been very important progress in oncology,with new and more effective chemotherapeutic agents administered alone or in combination improving the resectability rate in up to 40%of patients with colorectal liver metastases.Advances in interventional radiology,in particular,with the use of portal vein embolization and radiofrequency thermal ablation are new strategies allowing major liver resections and treatment of small liver metastases or early recurrences.Surgery,however,remains the gold standard strategy with intention to treat.In this review article we will describe the advanced role of surgery in the multidisciplinary approach to colorectal liver metastases,and the clinical problems the liver surgeon has to deal with,such as theresectability of the metastases,the presence of bilobar liver lesions and extrahepatic disease,the impact of chemotherapy in already resectable liver metastases,the problem of vanishing metastases after chemotherapy and the dilemma of staged or combined liver and colon operations and which organ first in the clinical scenario of synchronous colorectal liver metastases.

Neoadjuvant chemotherapy for colorectal liver metastases:A contemporary review of the literature

Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the only opportunity for cure and long-term survival.Over the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative care.Chemotherapy in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents.The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery.Consequently,the use of neoadjuvant strategies is becoming progressively more established.For patients with CRLM,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic resection.On the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy.Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative risk.Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability.In light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

Management of single pulmonary metastases from colorectal cancer:State of the art

Colorectal cancer(CRC)is one of the most common causes of death from cancer.Lung seeding occurs in approximately 10%of patients surgically treated for primary CRC with radical intent:the lung is the most common site of metastases after the liver.While surgical treatment of liver metastases is widely accepted to affect long-term outcomes,more controversial and not standardized is the therapy for CRC patients developing lung metastases.Experience suggests the potential curative role of pulmonary metastasectomy,especially in oligometastatic disease.However,the optimal strategy of care and the definition of prognostic factors after treatment still need to be defined.This review focused on the uncommon scenario of single pulmonary metastases from CRC.We explored pertinent literature and provide an overview of the epidemiology,clinical characteristics and imaging of single pulmonary metastases from CRC.Additionally,we identified the best available evidence for overall management.In particular,we analyzed the role and results of locoregional approaches(surgery,radiotherapy or ablative procedures)and their integration with systemic therapy.