Colorectal carcinoma with potentially resectable metastases: factors associated with the failure of curative schedule

BACKGROUND: The management of patients with colorectal cancer (CRC) and synchronous liver metastases (SLM) depends on the primitive tumor, resectability of the metastatic disseminations and the patient's comorbid condition(s). Considering all patients with potentially resectable primary CRC and SLM, curative resection (R0) will be possible in some patients, although in others surgery will never be performed. The purpose of our study was to identify factors of failure of the curative schedule in these patients. METHODS: We reviewed the data of patients with CRC and SLM between January 2002 and March 2007. Two groups were defined: group R0 when complete metastatic and primary tumor resection was finally achieved after one and more surgical stages and group R2 when curative resection was not possible at the end of the schedule. Clinical, pathologic and outcome data were retrospectively analyzed as well as preoperative management of SLM (chemotherapy, radiofrequency, portal vein embolization). RESULTS: Forty-five patients were included. Curative resection (group R0) was performed in 31 patients (69%) with 48% undergoing major hepatic resection. Mortality of hepatic resection was 0% although it was 9% for primitive tumor. Portal vein embolization was performed preoperatively in eight patients and radiofrequency ablation in 13. Median follow-up was 21 months. Overall survival was 86% at one year and 39% at three years. Survival in group 1 was 97 and 57% at one and three years respectively. Disease-free survival was 87 and 40% at one and three years. Tumor recurrence was noted in 61% of resected patients. At multivariate analysis, number of hepatic metastases superior than three and complicated initial presentation of primitive tumor were found to be significant and predictors of failure of hepatic resection. CONCLUSION: Aggressive management with curative resection of SLM may enable long-term survival. More than three SLM and complicated initial presentation of primitive tumor are factors predictive of failure of the curative schedule.     

Hepatic resection in stage IV colorectal cancer: prognostic predictors of outcome

Background and aims Hepatic resection has been proposed as an effective way to treat metastatic colorectal carcinoma. The aim of the study was to determine if contemporary resection of intestinal primary tumor and hepatic metastases is effective in the treatment of patients with metastases that are recognized at the initial clinical presentation of the primary tumor.Methods In a retrospective study, univariate and multivariate models were used to analyze the effect of patient demographics, tumor characteristics, and treatment factors on early and long-term outcome of patients submitted to synchronous intestinal and hepatic resection for colorectal liver metastases. From 1988 to 1999, 78 patients underwent surgical resection of primary colorectal tumor and hepatic metastases with curative intent. Criteria for study recruitment included primary tumor controllable, no extrahepatic disease detectable, and negative surgical margins of hepatic resection.Results The univariate analysis disclosed as adverse predictors of the long-term outcome the numbers of metastases (3; >3), pre-operative CEA value >100 ng/ml, resection margin <10 mm, and portal nodal status. Multivariate analysis confirmed number of metastases, resection margin and portal nodal status as independent predictors.Conclusions Our findings confirm hepatic resection as an effective procedure when undertaking combined bowel and hepatic resection. The applicability and the outcome of this surgical strategy is definitively influenced by the chance of a radical resection of the primary tumor, the number of hepatic metastases, resection margin wider than 1 cm, positive portal nodes, and the absence of any extrahepatic metastatic disease.     

Survival after resection of liver and lung colorectal metastases in the era of modern multidisciplinary therapy

Purpose

Despite recent improvement of the outcomes of colorectal cancer (CRC), the benefits of resection and appropriate selection criteria in patients with both liver and lung metastases remain controversial. The aim of this study was to analyze the outcomes and prognostic factors for survival in patients who underwent both hepatic and pulmonary resection for CRC metastases in the era of modern multidisciplinary therapy.

Methods

A retrospective analysis of 43 consecutive patients who underwent both liver and lung resections for metastatic CRC at our institute from 2003 to 2011 was performed. All patients in this study had achieved cancer-free status after resection of the second metastatic site.

Results

Of the patients, 24 (56 %) had synchronous metastatic disease with their primary tumor. Twenty-seven patients had developed recurrence after resection of the second metastatic site. In 14 cases, re-metastasectomy was performed for recurrence. Fourteen patients received palliative chemotherapy after recurrence, and all of these patients received oxaliplatin and/or irinotecan-based chemotherapy. After resection of the second metastatic organ, the 5-year relapse-free and overall survival rates were 29.6 and 70.0 %, respectively. Patients with multiple lung metastases had worse relapse-free survival than patients with solitary lung metastases at first lung resection (p?=?0.046).

Conclusions

Aggressive surgical resection and a combination of modern chemotherapeutic agents improve the survival of patients with lung and liver metastases from CRC. The presence of multiple lung metastases at resection suggests a poor prognosis.     

Liver metastases

Opinion Statement Liver metastases, especially from colorectal primary cancers, are treatable and potentially curable. Imaging techniques such as CT, MRI, and sonography have advanced in recent years and led to increased sensitivity and specificity in the diagnosis of liver metastases. Liver surgery also has been revolutionized in the past two decades. Dissections along nonanatomic lines have permitted the resection of multiple lesions that previously might have been considered unresectable. We regard resection of a solitary hepatic metastasis or up to four metastases from colorectal carcinoma as the best treatment for this condition. In patients over 70 years of age and those with medical conditions preventing surgery, we endorse expectant follow-up as long as the tumor remains stable. But if the tumor begins growing rapidly and local techniques cannot be used, we consider systemic chemotherapy. In patients with progressive metastatic liver disease, we initiate systemic therapy or hepatic arterial infusion. In young patients with metastatic disease, even when the disease is indolent or symptomatic, it may be difficult not to treat. We use either local regional therapy (resection or regional infusion) or systemic chemotherapy followed by regional therapy. In patients with neuroendocrine tumors metastatic to the liver, the first approach we use is not to treat because there may be a long period of stable disease. We use Sandostatin (Sandoz Pharmaceuticals, East Hanover, NJ) to treat symptoms. If the tumor progresses and symptoms cannot be controlled, these vascular tumors can be treated by embolization or chemoembolization, with high expectations of response. Newer approaches to liver metastases such as cryosurgery, chemoembolization, and interstitial radiation are also available. Cryosurgery is an ablative procedure that has not been proven yet to be as effective as surgical removal of metastases. However, in a situation where surgery cannot be performed, cryosurgery is an alternative. Chemoembolism has not been proven to be more effective than systemic therapy for liver metastases, but it allows another regional approach. External localized radiation can be used for patients who fail first-line treatment or in new protocols to delineate its value, perhaps in concert with chemotherapy. We also consider offering external localized radiation in patients who fail first-line treatment, perhaps in concert with chemotherapy. The usefulness of these techniques compared with surgery or regional therapy is being investigated.     

Rationale of the so-called extended resection for pancreatic invasive ductal carcinoma

It has generally been recognized that for adenocarcinoma of the pancreas, surgical resection provides the only chance for cure. In this study, we have analyzed the long-term survival of 141 patients with invasive ductal adenocarcinoma of the pancreas who received macroscopically curative resection. Multivariate analysis demonstrated that comprehensive stage of the tumor, curability of the resection, and adjuvant radiation therapy were independent prognostic factors. Pancreatectomy in this study was done with an extensive retroperitoneal clearance of para-aortic lymph node and nerve tissues, so-called extended resection. Survival curves of these patients revealed that the R0 resection is essentially necessary for long-term survival. Survival curve without microscopic lymph node metastasis was significantly better than that with node metastasis; however, 3 patients with node metastasis have been alive for more than 3 years. The survival curve of the patients who received adjuvant radiation therapy was better than of those who underwent surgery alone, and postoperative regional chemotherapy with continuous 5-FU infusion decreased hepatic metastases within 6 months. The results suggest that local recurrence of pancreatic cancer might possibly be controlled by extended resection and adjuvant irradiation, and early development of hepatic metastases might be controlled with regional chemotherapy.     

Kurativer Ansatz für metastasierte kolorektale Karzinome

Synchronous or metachronous metastases of colorectal cancer (CRC), although being the expression of systemic disease, allow a curative approach for a selected group of patients. Mainly patients presenting with colorectal liver metastases (CLM) should be evaluated for multimodal management with curative intent. Preoperative and/or postoperative systemic chemotherapy show beneficial impact on progression-free and overall survival, without significantly increasing postoperative complication rates. Concerning the complex definition of resectability and the number of patients with ?borderline“ resectable CLM, preoperative chemotherapy plays an important role in both improvement of prognosis and ?conversion“ to a resectable status. Advances in hepatic surgery and the addition of either locally ablative procedures, such as radiofrequency and SIRT are extending resectability to a larger group of patients and have joined the armamentarium for cases of positive resection margins or technically unresectable disease or add to surgery with a large loss of liver parenchyma. Moreover, multimodal approaches should be considered in pulmonary and peritoneal metastases of CRC.     

Chemotherapy of primary and secondary liver tumors

Liver is the most common site of metastatic disease. Although primary liver tumors are relatively rare in the Czech Republic, liver tumors represent a frequently encountered problem because of high incidence of colorectal and pancreatic cancer. Regimens of systemic chemotherapy or biologic therapy are used for secondary liver tumors according the primary site. It was demonstrated in randomized clinical studies that some of these regimens significantly prolong survival. Although only palliative therapy is possible for most of the patients with liver metastases, resection should be considered in patients with isolated liver involvement. Liver resection represents a curative approach and long-term success seems to be enhanced by neoadjuvant (preoperative) chemotherapy or adjuvant (postoperative) hepatic arterial chemotherapy. Hepatic arterial chemotherapy is also effective in the palliative treatment of unresectable liver metastases. Although it is still uncertain whether hepatic arterial chemotherapy increases survival of patients compared to systemic chemotherapy, it may be regarded as the best available treatment in selected patients because of better palliation associated with higher objective response rate and less systemic toxicity. Along with systemic and hepatic arterial chemotherapy, other approaches are being currently investigated in the treatment of primary and secondary liver tumors, including the use of biologic agents, agents with non-cytotoxic mechanism of action, or chronomodulated chemotherapy.     

Long-term disease free survival in a patient with metastatic adreno-cortical carcinoma after complete pathological response to chemotherapy plus mitotane

Adreno-cortical carcinoma (ACC) is a rare cancer with poor prognosis. Complete surgical resection of the primary tumor and, when feasible, of the local and distant metastases offers the best prospects for long-term survival; conversely, the role of systemic therapy in patients developing unresectable metastatic disease is unclear. We describe the case of a young female patient (36 yr) who presented with an androgen-releasing metastatic ACC. Treatment consisted of five courses of chemotherapy with etoposide, doxorubicin and cisplatin (EDP scheme) plus oral mitotane, which caused the complete disappearance of distant metastases and reduction of the primary tumor, as documented by serial computed tomography (CT) scans of the chest and the abdomen. Moreover, during treatment, clinical and biochemical resolution of the hypersecretory status occurred. The left adrenal gland was then removed and histopathological examination showed extensive tumor necrosis and the absence of viable cancer cells. The patient is currently alive without evidence of recurrence 3 yr after surgery. This report shows that chemotherapy plus mitotane could result in complete pathological remission, which may be a surrogate for long-term progression- free survival in metastatic ACC patients.     

Colorectal cancer metastases: surgical indications and multimodal approach

BACKGROUND/AIMS: The therapeutic plan to follow in patients affected by hepatic and pulmonary metastases from colorectal cancer is based on prognostic factors and staging. METHODOLOGY: Our experience from January 1980 to January 2002 underlines the effectiveness of combined multimodal therapy in the treatment of advanced metastatic stages. A total of 224 patients with metastases from colorectal cancer have been treated. Among these patients 160 underwent surgery (4 pulmonary and 156 hepatic resections), 17 have been reoperated for metastatic relapse, 14 with multiple metastases underwent locoregional therapy, while 33, deemed not resectable initially, have been treated with neoadjuvant chemo- and radio-therapy. RESULTS: For the operated patient group the 5-year actuarial survival was 22% with an operative morbidity of 17.5% and mortality of 3.8%. The 17 patients reoperated for metastatic relapse had a 5-year actuarial survival of 21% with an operative morbidity of 11.6% and mortality of 5.8%. The 14 patients treated with locoregional therapy had a median survival of 6 months whereas the 33 patients treated with combined multimodal treatment in two different periods had a response rate of 57.57%. Five patients had a complete response and 4 are presently alive: 3 are disease free and 1 with disease. 1 died of pulmonary primitive neoplasm 24 months later. CONCLUSIONS: Surgical resection is presently the best known treatment for metastatic disease. In advanced, but not yet disseminated, stages in which there is no indication to surgery on metastases (II-III stages according to Gennari's classification), a neoadjuvant treatment is proposed, if the primary tumor has already been completely resected. This therapeutic strategy, called combined multimodal therapy, has the aim to obtain the disease regression and to offer the chance of disease re-staging.     

Adjuvant chemotherapy for resected colorectal cancer metastases:literature review and meta-analysis

Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.     

Chemotherapy for the conversion of unresectable colorectal cancer liver metastases to resection

Resection of colorectal liver metastases (CLM) is the ultimate aim of treatment strategies in most patients with liver-confined metastatic colorectal cancer. Long-term survival is possible in selected patients with initially resectable or unresectable CLM. As a majority of patients have unresectable liver disease at the outset, there is a clear role for chemotherapy to downstage liver disease making resection possible. Studies of systemic chemotherapy with or without biologic therapy in patients with unresectable CLM have resulted in increased response rates, liver resection rates and survival. A sound physiologic rationale exists for the use of hepatic arterial infusion (HAI) therapy. Studies have shown that HAI with floxuridine combined with systemic chemotherapy increases response rates and liver resection rates in those patients with initially unresectable CLM. Toxicity from preoperative chemotherapy, biologic therapy and HAI therapy may adversely affect hepatic resection but can be kept minimal with appropriate monitoring. All conversion strategies should be decided by a multidisciplinary team.     

结直肠癌肝转移的综合治疗策略

结直肠癌(colorectal cancer,CRC)是世界上常见的消化道肿瘤之一,约有50%的患者最终出现肝转移。对于发生肝转移的患者,若不经治疗,中位生存期仅为6.9个月,5年生存率为0。若肝脏转移灶行根治性手术,则中位生存期为35个月,5年生存率为30～50%,因此手术切除仍是结直肠癌肝转移治疗的首选。对于同时性肝转移的患者,若无肠道梗阻、穿孔、出血等症状,笔者倾向于同时性切除原发灶和转移灶,术中联合应用B超探查、微波、射频等新技术来提高切除率,降低复发率。而临床上只有少部分患者(10%～15%)可以行手术治疗。对于不可切除的肝转移灶,需通过多学科讨论,针对疾病某一时期,制定出详细的个体化综合性治疗方案,如术前新辅助化疗、联合靶向药物治疗、门静脉栓塞术的应用、局部治疗、放疗等,使得一些不可切除的病灶转化为可切除病灶。因此癌肿作为一项全身性疾病,单纯依靠一种治疗手段很难取得理想的效果,需要多学科的合作,通过对疾病的不同时期进行认识、讨论,以便找到针对某一时间段疾病的最佳治疗方法。同时术后需要定期复查及时发现复发和转移以及制定进一步治疗计划,从而提高患者的长期生存率及生活质量。     

Die medikament?se Therapie des kolorektalen Karzinoms

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Almost every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics in the past decade has significantly improved the systemic treatment of patients with CRC. In stage III colon cancer combination chemotherapy with oxaliplatin is the standard of care. In stage IV cancer the choice of therapy is dependent on the clinical status of the patient. For some patients primary resection of metastases or resection after combination therapy and downsizing of lesions offers a chance for cure. In the palliative setting intensive combination treatment is indicated if the patient suffers from tumor related symptoms or a rapid progress of the disease. The aim of palliative therapy is the prolongation of survival and the improvement of quality of life. Combination with monoclonal antibodies leads to further improvement of survival. Furthermore, the introduction of the mutational status of the KRAS oncogene as the first predictive marker into clinical care is an important step towards the individualization of treatment in CRC.     

Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options

Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.     

Repeated liver resection for recurrent metastases from colorectal cancer

BACKGROUND/AIMS: Repeat hepatectomy is the most effective treatment for recurrent colorectal liver metastases. We aim to assess how repeated liver resections increase survival, without unacceptable surgical risk. METHODOLOGY: Between December 1992 and December 1998, among 19 patients, 5 underwent secondary resection of recurrent metastatic disease. Following the primary liver surgery, three patients had systemic chemotherapy with 5-fluorouracil and two locoregional chemotherapy via Port-a-cath in the gastroduodenal artery. We evaluated survival and we compared time of surgery, duration of Pringle maneuver, blood losses and postoperative stay in the hospital between first and second liver surgery. RESULTS: Perioperative mortality at second liver resection was nil; morbidity minor; mean duration of surgery 320 vs. 260 min; Pringle maneuver 35 vs. 25 min; blood losses 1300 vs. 650 mL; postoperative stay 12.6 vs. 11.5 days. Mean total survival from time of colon resection was 50 months. As an interesting secondary finding, we observed prolonged inhibition of liver regeneration following treatment with Methotrexate. CONCLUSIONS: Repeated hepatic resection is a safe procedure for selected patients. Surgical risk is slightly increased, but the risk/benefit ratio is definitely in favor of as many repeated resections as needed, whenever there is a chance of curative surgery.     

Does the site of primary colorectal cancer influence the outcome after resection of isolated liver metastases?

IntroductionIn unresectable patients with metastatic colorectal cancer (CRC), the site of the primary is a strong prognostic factor warranting major adjustments in palliative medical treatment. Initial results suggested that the site of CRC influences prognosis after curative resection of colorectal liver metastases (CLM). In this study, we evaluated outcome after resection of isolated CLM with regard to the location of the primary.Methods221 patients with macroscopically complete resection of CLM and no known extrahepatic disease were identified. 63 patients had right-sided and 158 had left-sided CRC. Tumors of the transverse colon and rectum were excluded. Survival was evaluated using the Kaplan–Meier method.ResultsCharacteristics of CLM, primary tumor stage and chemotherapeutic regimens were not significantly different between the two groups. Kaplan–Meier five-year survival was comparable (41%) in patients with right- or left-sided CRC (p = 0.64). Microscopic resection margin, number of liver metastases, age and nodal status but not the site of the primary tumor significantly influenced survival.ConclusionThe site of the colorectal primary in this well-defined group of patients after resection of isolated CLM did not prove to be of significant prognostic value. Whether the primary tumor in CLM is located on the left side or the right should not preclude patients from surgery.     

Operative Therapie des Nierenzellkarzinoms

The aim of surgical treatment for renal cell carcinoma is complete resection of the tumor. For localized renal cell carcinoma organ-sparing resection of the kidney tumor has become the gold standard, in particular for preservation of renal function with comparable oncological efficacy compared to radical nephrectomy. Crucial for the organ-sparing approach is currently the judgment of the surgeon whether a complete resection is possible. Organ-sparing renal tumor surgery can be performed with the appropriate expertise by minimally invasive laparoscopic, retroperitoneoscopic or robot-assisted (??da Vinci??) approaches. Alternatively various other treatment options, such as radical nephrectomy, percutaneous or laparoscopic thermal ablation or active surveillance are available. The therapeutic approach should be discussed individually with the patient and in addition to the oncologic issues, comorbidities, life expectancy and renal function must also be taken into account. For locally advanced renal cell carcinoma complete resection of the tumor is the method of choice. In metastatic renal cell carcinoma in the context of a multimodal treatment prior to systemic therapy cytoreductive nephrectomy is advised. The role of surgery in metastatic renal cell carcinoma remains unchanged in the era of targeted therapy. Patients with solitary or surgically manageable metastases should be considered for metastatic surgery with curative intent in order to avoid the toxicity of systemic therapy.     

Renal cell carcinoma: current status and future directions

Although renal cell carcinoma accounts for only 3% of adult malignancies, it has been increasing in incidence by 2-4% per year since the 1970's. Cigarette smoking, obesity and end-stage renal disease are important risk factors. Genetic syndromes such as von Hippel-Lindau disease are also associated with an increased incidence of renal cell carcinoma. Localized disease should be treated with surgical resection. However, approximately 30% of patients present with metastatic disease. Complete resection of metastases can result in long-term survival in some individuals. Removal of the primary renal tumor in patients with unresectable disseminated disease has also been shown to improve survival in selected good performance status patients receiving systemic immunotherapy. While chemotherapy has been relatively ineffective in the treatment of renal cell carcinoma, biologic therapy with interleukin-2 or interferon does lead to responses in a minority of patients, with occasional long-term survivors. Recently, promising results have been reported with allogeneic stem cell transplantation using a non-myeloablative conditioning regimen. However, therapy for metastatic renal cell carcinoma remains inadequate. Ongoing trials with novel approaches such as anti-angiogenesis agents, cyclin-dependent kinase inhibitors, and tumor vaccines will hopefully lead to improved outcomes in this disease.     

A rare surgical case of multiple liver resections for recurrent liver metastases from pancreatic gastrinoma: liver and vena cava resection

Pancreatic gastrinoma is a rare non-β islet cell tumor. Approximately 60% of gastrinomas are malignant; despite the fact that they are usually slow growing, liver metastases have a major impact on prognosis. Most authors have advocated aggressive surgical management as being the only potentially curative therapy to improve survival as well as to provide outstanding relief from symptoms. We present a case of a 57-year-old man referred to our hospital with a diagnosis of liver metastases from pancreatic gastrinoma, with suspected involvement of the inferior vena cava (IVC). At the age of 37 years, he was diagnosed in his local hospital as having a pancreatic gastrinoma, with liver metastases, and he underwent distal pancreatectomy, splenectomy and enucleation of liver metastases. A liver tumor recurred twice, 7 and 9 years after the first surgery, for which double liver resections were performed: the first time he underwent enucleation of multiple liver metastases in segments II, III, IV, V, VI, VII and VIII, with resection of the right hepatic vein and partially resection of the diaphragm; the second time he underwent enucleation of multiple liver metastases in segments II, III, IV, and V. In our hospital, 8 years after the last surgery, the patient underwent right extended trisectionectomy, resection of segment I, combined resection of the IVC, and partial removal of the diaphragm. To the best of our knowledge, from a review of the literature, this is the first case to achieve successful long-term survival through aggressive surgical management of this type of metastatic endocrine tumor. The patient described here is still alive, free of disease and leading a normal life, 20 years after the initial diagnosis and 3 years after the last surgery.