Improving definition of the term “synchronous liver metastases” from colorectal cancer

正The liver is the most frequent site of metastasis in colorectal cancer with up to a quarter of patients having liver metastases at the time of initial diagnosis and a further third subsequently developing liver lesions.~([1])Patients who present with metastatic liver disease after treatment of the primary(termed metachronous disease)receive care focused on this new metastatic disease.~([2])In contrast,the management of patients who present with colorectal cancer and concurrent liver     

Is hepatic resection for multiple liver metastases from colorectal carcinoma acceptable treatment?

BACKGROUND/AIMS: To determine an appropriate surgical treatment for patients with multiple liver metastases, we evaluated the efficacy of treatment in patients with 5 or more liver tumors in both lobes after metastasis from colorectal carcinoma which we refer to as H3 liver metastasis. METHODOLOGY: Seventy-two cases of H3 liver metastasis were classified as follows into four types according to tumor distribution in the liver: type A (n = 16), multiple metastases present in one lobe, and, in the other, confined to one segment; type B (n = 12), multiple metastases present bilaterally, but with tumors larger than 2 cm in diameter confined to one lobe or to three segments; type C (n = 10), multiple and diffuse metastases present in both lobes and all tumors 2 cm or less in diameter; and type D (n = 34) metastatic tumors larger than 2 cm in diameter occurring in every segment of the both lobes. Hepatectomy was performed within a possible range as a rule for all cases, and intrahepatic arterial infusion was performed in unresectable cases. In cases that responded to intrahepatic arterial infusion, hepatectomy was considered and performed when technically possible and potentially curative. RESULTS: The proportion of cases treated with hepatectomy were: type A, 56.3%; type B, 8.3%; type C, 10.0%; and type D, 2.9%. The regional intrahepatic arterial infusion ratios and response rates to it were 18.8% and 0.0% in type A, 91.7% and 33.3% in type B, 80.0% and 71.4% in type C, and 64.7% and 0.0% in type D, respectively. One type B patient whose tumor showed complete resolution after intrahepatic arterial infusion and one type C patient with a partial response underwent hepatectomy. The cumulative survival rate at two years was significantly lower in type D (3.2%), than in the other types (type A, 33.3%; type B, 36.4%; and type C, 11.7%). CONCLUSIONS: These results suggested that hepatectomy should be performed in cases of type A, and that intrahepatic arterial infusion may be effective as neoadjuvant chemotherapy for type B or C. However, there is no effective treatment for type D at present.     

Is CA19-9 effective in predicting chemotherapeutic response in patients with synchronous liver metastases with colorectal cancer?

Evaluation of response to chemotherapy in colorectal cancer patients with synchronous liver metastases is important in terms of treatment management.In this Letter to the Editor,several issues in the article are discussed.For the comparison of carbohydrate antigen 19-9(CA19-9)values referenced in the study,the patient group was not matched for cancer stage.Therefore,it may be more appropriate to select and compare CA19-9 values in patients with same-stage cancer.     

Treatment strategy for colorectal cancer with resectable synchronous liver metastases:Is any evidence-based strategy possible?

Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor:published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre’s experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to evidence-based medicine and to adopt a sort of experience-based medicine. Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primarytumor in situ , even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment’s schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient’s selection, disease control and safety and completeness of surgery.     

Treatment of liver metastases from colorectal cancer: what is the best approach today?

Liver is the common site for metastases from colorectal cancer. The 5-year overall survival rate of patients following radical operations is 25%. Surgery can be carried out in only 10-15% of the patients, yet it remains the potential curative treatment for resectable lesions. For the unresectable cancers, only chemotherapy is recommended. New drugs such as Irinotecan prolongs the overall survival of patients affected by advanced disease. In patients with unresectable metastases at diagnosis, pre-surgical treatment with Oxaliplatin leads to reduction of the lesions, allowing resection in 16% of cases. Chemotherapy may be delivered directly into the liver via the hepatic artery. No, clinical trials, to date, have shown convincing survival results in patients treated with this procedure. Combined hepatic artery and systemic treatment may provide a new strategy as adjuvant therapy for patients undergoing resections.     

Hormone receptor status of primary tumor as a prognostic factor in patients with liver metastases from breast cancer treated with transcatheter arterial chemoembolization

TO THE EDITOR We read with great interest the article by XP et al. They reported the results of their experience with transcatheter arterial chemoembolization (TACE) and systemic chemotherapy for forty-five patients with liver metastases from breast cancer and evaluate the prognostic factors. In their study, the response and survival rates were significantly better in TACE group than in chemotherapy group. The lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were found to be significandy associated with survival in both univariate and multivariate and analyses.     

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 > 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.     

On or in the liver? Two cases with diffuse pseudomyxoma peritonei and synchronous hepatic pathology

Pseudomyxoma peritonei (PMP) is a borderline malignancy, simulating carcinomatosis and generally arising from perforation of an appendiceal mucinous tumour. Some patients have coincidental dual pathology. Liver abnormalities in particular may be overlooked and/or misclassified. We report 2 cases of patients who had diffuse PMP with synchronous hepatic pathology to highlight the need for vigilance and appropriate assessment of coincidental liver lesions. An assessment and management strategy is outlined.     

When should a liver resection be performed in patients with liver metastases from neuroendocrine tumours? A systematic review with practice recommendations

Aim

To determine the benefits and risks of hepatic resection versus non-resectional liver-directed treatments in patients with potentially resectable neuroendocrine liver metastases.

Methods

A systematic review identified 1594 reports which alluded to a possible liver resection for neuroendocrine tumour metastases, of which 38 reports (all retrospective), comprising 3425 patients, were relevant.

Results

Thirty studies reported resection alone, and 16 studies reported overall survival (OS). Only two studies addressed quality-of-life (QoL) issues. Five-year overall survival was reported at 41–100%, whereas 5-year progression-free survival (PFS) was 5–54%. We identified no robust evidence that a liver resection was superior to any other liver-directed therapies in improving OS or PFS. There was no evidence to support the use of a R2 resection (debulking), with or without tumour ablation, to improve either OS or QoL. There was little evidence to guide sequencing of surgery for patients presenting in Stage IV with resectable disease, and none to support a resection of asymptomatic primary tumours in the presence of non-resectable liver metastases.

Conclusion

Low-level recommendations are offered to assist in the management of patients with neuroendocrine liver metastases, along with recommendations for future studies.     

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer—a monocentric analysis

Purpose

The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible.

Methods

We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution.

Results

Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p?<?0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p?<?0.0001), but not in PFS (p?=?0.635). Patients with ≤?4 distant metastases showed a better OS (p?=?0.033).

Conclusions

Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.

     

“Liver‐first” approach for synchronous colorectal liver metastases: is this a justifiable approach?

Background

To review the outcomes of patients with synchronous colorectal liver metastases (CRLM) treated by the “liver-first” approach.

Methods

Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords “colorectal cancer”, “liver-first”, “reverse strategy”, “liver metastases”, “liver resection” and “hepatectomy”.

Results

There have been four retrospective studies that have reported the outcomes of patients with synchronous CRLM following the reverse strategy. The number of patients included ranged from 16 to 27. One study included patients with advanced rectal cancer and synchronous liver metastases only. None of the studies defined resectability for the CRLM. Overall, the morbidity and mortality rates were low. The recurrence rate ranged from 25 to 70 %. One study did not report survival data, and the overall 5 year survival ranged from 31 to 41 %.

Conclusion

The “liver-first” approach may be beneficial to a selected group of patients with synchronous CRLM. Patient selection is likely to be determined by their response to down-staging chemotherapy with or without biological agents.     

Would smokers with schizophrenia benefit from a more flexible approach to smoking treatment?

We evaluated literature that addresses the notion that flexible smoking treatment approaches are warranted for smokers with a diagnosis of schizophrenia. Understanding the biological and psychological mechanisms that increase the likelihood of smoking and decrease the motivation to quit for these individuals is addressed within the framework of a neurobiological model. We provide a brief overview of the limited smoking cessation treatment literature for patients with schizophrenia and compare abstinence-focused versus reduction-focused treatment modalities. The potential utility of the reduction-focused approach to tobacco treatment for these smokers is evaluated. Suggestions for future research to address the utility and efficacy of reduction-focused interventions for smokers with schizophrenia are put forth. We conclude with a consideration of the implications for the current understanding of smoking treatment among patients with co-morbid psychiatric diagnoses.     

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

AIM:To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS:Nine hundred and sixteen patients with brain metastases,treated with whole brain radiation therapy (WBRT)between January 1985 and December 2000 at the Department of Radiation Oncology,University Hospital Freiburg,were analyzed retrospectively. RESULTS:Fifty-seven patients presented with a primary tumor of the gastrointestinal tract(esophagus:n=0,stomach: n=10,colorectal:n=47).Twenty-six patients had a solitary brain metastasis,31 patients presented with multiple brain metastases.Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray(Gy)or 3 Gy to a total dose of 50 Gy or 30 Gy,respectively.The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively(P<0.01,log-rank).Median overall survival for all patients with brain metastases(n=916)was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors(P<0.05,log-rank).In patients with gastrointestinal neoplasms(n=57),the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases(P<0.01,log-rank).The median overall survival for patients with a Karnofsky performance status(KPS)≥70 was 5.5 mo vs2.1 mo for patients with KPS<70(P<0.01, log-rank).At multivariate analysis(Cox Model)the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION:Brain metastases occur late in the course of gastrointestinal tumors.Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.     

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy： Prognostic factors and survival

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P&lt;0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P&lt;0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P&lt;0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS &lt;70 (P&lt;0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.     

Pseudocirrhosis in a pancreatic cancer patient with liver metastases： A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin （GEMOX）. After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen （CEA） and CA19 by 〉 50% and nearly complete resolution of hepatic metastases in computed tomography （CT） scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.     

Surgical treatment of liver metastases of gastric cancer: is local treatment in a systemic disease worthwhile?

Objectives

The prognosis of patients with liver metastases of gastric cancer (LMGC) is dismal, but little is known about prognostic factors in these patients; thus justification for surgical resection is still controversial. The purpose of this study was to review recent outcomes of hepatectomy for LMGC and to determine which patients represent suitable candidates for surgery by assessing surgical results and clinicopathologic features.

Methods

Outcomes in 21 patients with LMGC who underwent hepatectomy between 1998 and 2007 were assessed. Isolated metastases and potential to perform a curative resection were requisite indi-cations for surgery. Surgical outcome and clinicopathologic features of the hepatic metastases were analysed.

Results

Overall 1-, 3- and 5-year survival rates after hepatic resection were 68%, 31% and 19%, respectively; three patients survived for >5 years without recurrence. Univariate analysis revealed a solitary metastasis, negative margin (R0) resection and the presence of a peritumoral fibrous capsule as significant favourable prognostic factors. These characteristics were present in all of the three patients who survived for >5 years.

Conclusions

Solitary metastases from gastric cancer should be treated surgically and confer a better prognosis. Surgical resection should provide microscopically negative margins (R0). A new prognostic factor, the presence of a pseudocapsule, may be associated with improved prognosis.     

α2-Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver

Localization and production of alpha2-macroglobulin (alpha2M), a multifunctional binding protein with protease and cytokine scavenging properties, was studied in situ in rat livers containing experimentally induced colon carcinoma metastases by means of immunocytochemistry and in situ hybridization methods. The study was performed to investigate whether alpha2M production by hepatocytes plays a role in the defense against the growth of metastases on the basis of its protease inhibiting capacity. It was found that colon cancer cells in all developmental stages of the metastases contained large amounts of messenger RNA (mRNA) of alpha2M but hardly any alpha2M protein. Cancer cells in culture contained large amounts of both mRNA and protein of alpha2M. In contrast, stromal cells and liver cells did not show positivity for alpha2M mRNA above background levels. The exception was a few layers of hepatocytes around the latest stage of metastases. Hepatocytes contained both alpha2M mRNA and protein only when Kupffer cells were present, indicating that alpha2M mRNA production was induced via Kupffer cells. On the other hand, alpha2M protein was found in high amounts in the sinusoids and stroma of all metastases, irrespective of their developmental stage. Increased levels of alpha2M could not be detected in serum in all but one rat tested (n=8). It is concluded that production of alpha2M by hepatocytes occurs only around the latest developmental stage of metastases and that alpha2M does not play a significant role in the defense against metastatic cancer growth in rat liver. In contrast, cancer cells produce and secrete large amounts of alpha2M, which seems to be linked with their tumorigenicity. We suggest that this alpha2M captures cytokines rather than proteases by complex formation. These complexes were observed using immunocytochemical staining for alpha2M protein indicating that it was captured by either stromal cells, sinusoidal cells, or hepatocytes that are in direct contact with cancer cells, Therefore, changes in serum levels of alpha2M were limited, indicating that these levels do not reflect local production and effects of alpha2M. (Hepatology 1996 Mar;23(3):560-70)