Pulmonary Metastases Of Colorectal Cancer Research Articles

Carbonic anhydrase IX is associated with early pulmonary spreading of primary colorectal carcinoma and tobacco smoking

Pulmonary metastasectomy is performed routinely in selected patients with metastatic spreading to the lungs. According to current guidelines, the tumour biology should be taken into account when selecting patients for a resection. Carbonic anhydrase IX (CA9) expression has been shown to be a common feature in primary tumour growth and metastasis and it negatively affects the clinical outcome in various malignancies. Data on CA9 in pulmonary metastases are lacking. Forty-four patients with primary colorectal cancer (CRC) who underwent curative pulmonary metastasectomy were included in this study. We determined the expression of CA9 in pulmonary metastases and corresponding primaries by immunohistochemistry. The expression level was correlated with clinical parameters and patients' smoking habits. Furthermore, the impact of nicotine treatment on phosphorylation of STAT3, HIF-1α and CA9 expression was assessed in HT29 cells. High expression of CA9 in resected pulmonary metastases and corresponding primary tumours correlated with early spreading to the lung (both P < 0.001). Moreover, CA9 expression was affected by the smoking habits of the patients. Treating HT29 cells with nicotine resulted in an induction of CA9 in vitro. This induction was associated with STAT3 phosphorylation and was independent of HIF-1α. This study provides first evidence of CA9 expression in pulmonary metastases of CRC and suggests a role of CA9 as a prognostic marker. Moreover, our in vitro and in vivo data indicate an association between tobacco smoking and CA9 expression. Immunohistochemical assessment of CA9 expression might serve as an additional tool in decision-making for selecting patients for pulmonary metastasectomy.

Outcomes after pulmonary metastasectomy for colorectal cancer

Surgical resection offers the greatest likelihood of cure for appropriately selected patients with pulmonary colorectal carcinoma metastases. We hereby report our experience over the last 19 years at the Austin Hospital, Thoracic Surgery Unit. This is a retrospective study of a consecutive series of patients with pulmonary colorectal cancer metastases. From 1994 to 2012, 66 patients underwent 83 pulmonary metastasectomies for colorectal cancer at the Austin Hospital. Seventy per cent of patients were operated on for single pulmonary metastases. The most common procedure performed was a video-assisted thoracoscopic surgery wedge resection. Median follow-up duration was 25 months. Three-, five-, seven- and ten-year survival was 53.4, 39.6, 34.6 and 23.1%, respectively. Pulmonary metastasectomy for metastatic colorectal carcinoma continues to offer the greatest survival advantage for appropriately selected patients.

Long‐term survival after hepatic and pulmonary resection of colorectal cancer metastases

Recent changes in adjuvant therapies improved the prognosis of metastatic colorectal cancers. Curative resection may be considered, even for both pulmonary and hepatic metastases, but prognostic factors are not well identified. From 1995 to 2010, 69 patients had curative resection of pulmonary metastases of colorectal cancer; 31 had also hepatic metastases. Pulmonary and hepatic resection occurred in 2 steps (87%). We studied overall and disease-free survival and prognostic factors. Primary tumor location was the rectum in 10 cases (32%). Pulmonary metastases were synchronous in 5 (16%) and bilateral in 6 (19%). One patient (3%) died after pulmonary surgery. One (3%) had positive surgical margins for pulmonary metastases. Median overall survival was 44 months (5-year rate = 36%); median disease-free survival was 22 months (5-year rate = 10%). Factors linked to impaired survival were rectal primary tumor (P = 0.04) and bilateral pulmonary metastases (P = 0.02) for overall survival, and pulmonary metastase ≥ 20 mm (P = 0.04) for disease-free survival. When associated to adjuvant therapy, complete resection of pulmonary and hepatic metastases of colorectal cancer allows long-term survival in one third of the patients.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer.

e14533 Background: To determine impact of modern chemotherapy regimens after pulmonary metastasectomy from colorectal cancer (CRC). Methods: A total of 122 consecutive patients who curatively resected for pulmonary metastases of CRC in eleven oncology centers were retrospectively analysed between January 2000 and April 2012. Results: Of 122 patients, 108 who received chemotherapy with fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) combinations were analyzed. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). With a median follow-up of 14 months after metastasectomy, median recurrence-free survival (RFS) was 17 months, overall survival (OS) was not reached. Three and 5-years OS rates were 66% and 53%, respectively. There was no significant difference among cytotoxic regimens in respect to RFS and OS. Similarly, no significant difference was seen between BEV and NoBEV arms in respect to OS and RFS. In univariate analysis prior liver metastasectomy (p = 0.045), positive pulmonary margin (p = 0.028), disease-free interval &lt; 12 months (p = 0.013), and KRAS mutation (0.009) were negative significant prognostic for RFS. Thoracic pathological lymphatic involvement (p = 0.006) and higher prethoracotomy carcinoembryonic antigen (p = 0.038) were negative significant prognostic for OS. In multivariate analysis, positive pulmonary margin was the only negative independent prognostic for RFS, while thoracic lymphatic involvement was the only negative independent prognostic for OS. Conclusions: Chemotherapy type and addition of bevacizumab have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal pulmonary metastases.

Repeated Resection of Colorectal Cancer Pulmonary Oligometastases: Pooled Analysis and Prognostic Assessment

Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available. We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis. Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52% for patients who had 1 metastasectomy and 57.9% from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3cm were the only independent factors associated with inferior survival following repeated pulmonary resection. In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3cm have a significantly inferior survival.

Surgical treatment of synchronous and metachronous hepatic–and pulmonary colorectal cancer metastases —the Copenhagen experience

Background The surgical treatment of patients with isolated colorectal hepatic- or pulmonary metastases is well established with a 5-year survival in the range of 40–50 %. In contrast the treatment of patients with both hepatic- and pulmonary metastases remains controversial. We here present our initial results of patients who underwent both hepatic- and pulmonary resections for colorectal metastases with emphasis on post-operative complications and long-term survival.

Prognostic factors in patients undergoing complete resection of pulmonary metastases of colorectal cancer: a multi-institutional cumulative follow-up study

The aim of this retrospective study was to establish the prognostic factors for overall survival after pulmonary resection for lung metastases of colorectal carcinoma (CRC). The baseline characteristics and outcomes of 266 CRC patients undergoing complete pulmonary resection were collected from 19 institutions by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Study Group. We used the Cox proportional hazard regression to identify independent prognostic factors for OS. The 5-year overall survival rate of patients undergoing complete resection of isolated pulmonary metastases was 56.5 %. The independent unfavorable prognostic factors after pulmonary resection included stage T4 (p = 0.0004) and N2 (p = 0.0082) as primary cancer-related factors, and more than three metastases (p = 0.0342), bilateral distribution (p = 0.0450), metastatic disease-free interval (DFI) of less than 2 years (p = 0.0257), and a preoperative carcinoembryonic antigen (CEA) level greater than 5.0 ng/mL (p = 0.0209) as pulmonary metastases-related factors. This retrospective analysis suggested that the indications for pulmonary resection of CRC metastases should be decided not only by the status of lung metastases, but also by pulmonary-related factors such as the T and N stage of the primary lesion, preoperative CEA level, and the DFI.

Long-term results and prognostic factors after resection of hepatic and pulmonary metastases of colorectal cancer

Resection of colorectal liver or lung metastases is an established therapeutical concept at present. However, an affection of both these organs is frequently still regarded as incurable. All cancer patients are documented in our prospective cancer registry since 1995. Data of patients who underwent liver and lung resection for colorectal metastases were extracted and analysed. Sixty-five patients underwent surgery for liver and lung metastases. In 33 cases, the first distant metastasis was diagnosed synchronously to the primary tumour. For the remaining patients, median time interval between primary tumour and first distant metastasis was 18 months (5-69 months). Complete resection was achieved in 51 patients (79 %) and was less likely in patients with synchronous disease (p = 0.017). Negative margins (p = 0.002), the absence of pulmonary involvement in synchronous metastases (p = 0.0003) and single metastases in both organs (p = 0.036) were associated with a better prognosis. Five- and 10-year survival rates for all patients are 57 and 15 % from diagnosis of the primary tumour, 37 and 14 % from resection of the first metastasis and 20 and 15 % from resection of the second metastasis. After complete resection, 5- and 10-year survival rates increased to 61 and 18 %, 43 and 17 % as well as 25 and 19 %, respectively. Long-term survivors (≥10 years) were seen only after complete resection of both metastases. Patients with resectable liver and lung metastases of the colorectal primary should be considered for surgery after multidisciplinary evaluation regardless of the number or size of the metastases or the disease-free intervals. Clear resection margins are the strongest prognostic parameter.

Value of PET/CT Imaging for Diagnosing Pulmonary Metastasis of Colorectal Cancer

Several types of cancer can be clinically diagnosed by PET/CT, which can also perform whole-body imaging based on 18F-fluorodeoxyglucose (FDG) uptake. The present study assesses the value of PET/CT for diagnosing of pulmonary metastasis of colorectal cancer. We staged or restaged 256 patients with colorectal cancer by PET/CT. Actual and suspected pulmonary metastases were detected in 37 (male, n=23; female, n=14) patients with primary or recurrent colorectal cancer. Among them, 35 (21 males, 14 females) patients had extant homochronous (n=7) and metachronous (n=28) pulmonary metastasis. The sensitivity and specificity of FDG-PET/CT for pulmonary metastasis were 57.1% and 99.1%, respectively, and the positive and negative predictive values were 90.1% and 93.6%, respectively. The uptake of FDG was affected by the size of the metastatic nodules; uptake was positive and negative in pulmonary metastases with an average size of 14.9mm and 5.75mm, respectively. The limit of positive FDG uptake was reached in pulmonary metastases of about 9mm. Pulmonary metastasis of colorectal cancer can be accurately and conveniently diagnosed by PET/CT, especially when nodules are >9mm.

Optimal management of pulmonary metastases from colorectal cancer

The incidence of colorectal cancers is rising worldwide and pulmonary metastases were seen in approximately 10–15% of all patients. Surgical metastasectomy is a widely accepted procedure in selected patients and is considered as the only curative option in patients with secondary pulmonary malignancy. But surgical resection remains controversial due to the lack of randomized trials, comparing pulmonary metastasectomy to control, either medical therapy, or observation. This article will discuss the differentiated therapeutic strategies for patients with pulmonary metastases of colorectal cancer, focusing on surgical resection, patient evaluation, prognostic factors, interdisciplinary therapeutic approaches and current trials.

Liver transplantation for colorectal liver metastases: revisiting the concept

Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.

Factors Affecting the Outcome of a Pulmonary Resection for Metastatic Colorectal Cancer: Efficacy and Pitfalls

See Article on Page 354-358 Pulmonary resection of metastatic colorectal cancer is widely practiced in the field of oncologic surgery. However, only a highly selected subset of patients is eligible for resection, and the average recurrence rate is still high. According to general guidelines proposed by the UK National Institute for Clinical Excellence [1] and the National Comprehensive Cancer Network [2], however, for the following cases of metastatic pulmonary lesions, surgery is indicated: the metastases seem to be technically resectable, the general and functional risks are tolerable, the primary tumor is controlled, and no extrathoracic lesions are detected (with the exception of hepatic lesions for which both the hepatic and the pulmonary metastases can be completely removed). According to a review of the literature on surgical management of a pulmonary metastasis of colorectal cancer, the results vary depending on the selection criteria of individual surgeons or institutions. Due to the problems associated with a lack of randomized, prospective clinical studies, it remains difficult from an evidence-based perspective to assess or summarize the clinical usefulness of surgical management for metastatic lesions [3]. To date, however, most of the retrospective studies have demonstrated that a surgical resection of the pulmonary metastasis of colorectal cancer is a safe treatment modality with a lower degree of mortality. The following meta-analysis for a pulmonary metastasectomy in cases of colorectal cancer showed that for all 1,307 patients investigated, a minimum number of 40 cases with a mean follow up of 37.6 months, the overall 5-year survival was 40-68% after complete surgical resection, and the mean 5-year disease-free survival after complete resection was 19.5-34.4%. Recent reports reflect better treatment outcomes, but not come to the of all the patients [4]. Traditional risk factors and selection criteria are currently being discussed, but decision making presupposes a personalized strategy with predictive models. Such predictive models have a number of uses. In particular, due to the selection of patients who might benefit from such treatment modalities as neoadjuvant chemotherapy prior to a prethoracotomy, surgery, or active chemotherapies, those with good prognostic factors can receive the surgical treatment at earlier times and those with a poor prognosis are subject to delayed surgery. This delay, or trial of time, can allow a better assessment of additional disease and provide time for neoadjuvant therapy or more aggressive adjuvant therapy. Further, it can also be used to enroll patients who are at increased risks of recurrence in prospective randomized trials and can provide a postoperative surveillance strategy following the actual surgery [5]. On a multivariate analysis, Kanemitsu et al. [6] maintained that five prognostic factors, the primary histology, hilar or mediastinal lymph node involvement, the number of metastases, the preoperative level of the carcinoembryonic antigen, and extrathoracic disease, would be risk factors. These factors have a prognostic value for long-term survival, and related study models are advantageous in that the degree of clinical applicability is relatively higher. In addition, other prognostic factors affecting the survival rate following the pulmonary resection include a disease-free interval during which a diagnosis of pulmonary lesions is made. As shown in this study, however, there was no significant difference. In recent years, as a prognostic factor for pulmomary metastasis, genetic tests based on such technologies as the Affymetrix Gene Chip microarray have been applied. However, because of the prohibitive costs, reliance on frozen tissue, and advanced technical expertise required to use the technology, it is debatable whether such tests will ever be clinically applicable [7]. Thus, the immunohistochemical (IHC) staining profile can be a useful surrogate for gene expression analysis. Many studies have focused on the correlation between histopathologic and IHC measurements and survival [8, 9]. According to Shiono et al. [9] the histopathologic features of pulmonary metastases in 87 patients revealed the morphologic feature of an aerogenous spread with floating cancer cell clusters and vascular invasion at metastatic sites to be a prognostic factor of significance for survival. Lymphatic invasion or microsatellite instability of the primary tumor, however, has been reported to be unrelated to survival. Although smaller in number, with the recent advancement in molecular biological methods, ongoing studies are being conducted to examine the pulmonary metastasis of colorectal cancer. These studies will provide us further understanding of pulmonary metastatic cascade and allow patient treatment to be personalized.

Significance of Follow-up in Detection of Pulmonary Metastasis of Colorectal Cancer

PurposeThis study was performed to evaluate the effectiveness of conventional chest radiography, carcinoembrionic antigen (CEA) level and abdominal computed tomography (CT) or chest CT for early detection of pulmonary metastasis after a curative resection of colorectal cancer.MethodsWe retrospectively reviewed 84 cases of pulmonary metastasis from a group of colorectal cancer patients who had a curative surgical resection from 2000 to 2006 at the Korea University Medical Center.ResultsStage I tumors were detected in 4 patients, stage II tumors in 18, stage III tumors in 43 and stage IV tumors in 19. The detection rates for pulmonary metastasis were 28.5% by conventional chest radiography, 40.5% by increased CEA level and 28.5% by abdominal CT or chest CT. Among them, fourteen patients underwent a radical pneumonectomy. After detection of pulmonary metastasis, the survival outcome for the patients who underwent a resection of the lung was superior to the survival outcome of the patients who did not undergo a resection of the lung (43.7 months vs. 17.4 months, P = 0.001). For patients who underwent resections of the lung, pulmonary metastasis was detected by conventional chest radiography in 2 (14%) patients, by elevated CEA level in 6 (42%) patients, and by abdominal CT or chest CT in 6 (42%) patients.ConclusionConventional chest radiography is no more useful in detecting early pulmonary metastasis after a curative colorectal surgery than a routine chest CT. Thus, we propose the use of routine chest CT for screening for lung metastasis.

Efficacy of Surgical Resection of Both Pulmonary and Liver Metastases from Colorectal Cancer

Purpose: Resection is effective for some patients with isolated hepatic or pulmonary metastases of colorectal cancer (CRC). But the role of surgery in the management of patients who have both liver and lung metastases is not well defined. The aim of this study was to evaluate the validity of surgical therapy for isolated hepatic and pulmonary colorectal metastases. Methods: Between 1992 and 2006, 256 patients underwent hepatic resection for the first treatment of CRC metastases. Among these patients, 31 patients underwent both lung and liver resections for metastatic CRC. Demographic, perioperative, survival and variables were evaluated by retrospective chart review. Results: Twenty-nine patients (93.5%) underwent sequential pulmonary resection after hepatectomy because of recurrent disease. Two patients (6.5%) underwent staged liver and lung metastasectomy from synchronously identified metastases. Median interval between heaptic resection and pulmonary resection was 17.7±10.4 month. The features of the first liver metastases: The median number of tumors was 1.59 (range 1 to 20 tumors) and 14 patients had bilateral disease. The median size of the largest tumor was 3.0 cm (range 0.3 to 8 cm). In 11 (35.5%) patients, a hemihepatectomy or more was required to remove all gross disease. The features of the first pulmonary metastases: The median number of nodules was 2.7 (range 1 to 10) and 13 patients (41.9%) had their metastatic disease confined to bilateral lung. The median tumor size was 1.9 cm (range 0.4 to 6 cm). A large majority of patients (83.9%) had a wedge resection; lobectomy was required in only 5 (16.1%) patients. Median survival from resection of the first liver metastasis was 86.5 month, with the 5-, and 10-year over all survival rates of 77.5% and 39.5%, respectively. Median survival from resection of the first pulmonary metastasis was 55.2 month, with the 5-, and 10-year over all survival rates of 44.7% and 38.2%, respectively. By multivariate analysis, number of pulmonary metastases more than 3 (risk ratio= 4.417, 95% confidence interval CI=1.376-14.175, p=0.013) was an independent unfavorable prognostic factor of long-term survival. The overall cumulative survival results in patients with more than 3 pulmonary metastases (5,10-year 16.6 median survival 23.4 months) was markedly worse than in patients less than 3 pulmonary metastases (5-year 60.2%, 10-year 45.1% median survival 97.1 months) (p<0.0071). Conclusion: Surgical resection of both hepatic and pulmonary colorectal metastases is safe and results in excellent long term survival in selected patients. Poor results were obtained in patients who had more than 3 pulmonary metastases.

Outcome after Resection of Hepatic and Pulmonary Metastases of Colorectal Cancer

IntroductionMultimodal therapies (especially surgery of metastases and “aggressive” chemotherapy) in patients with metastases of colorectal cancers (CRC) are increasingly performed and may provide long-term survival in selected patients with more than one location of metastases. In the current literature, there are only few studies with relatively low patient numbers reporting on the outcome after resection of both hepatic and pulmonary metastases of CRC. We therefore evaluated survival of patients who underwent sequential resection of hepatic and pulmonary metastases under potentially curative intention. Material and MethodsFrom 1987 until 2006, 44 patients (32% female; median age, 58 years) with hepatic and pulmonary CRC metastases underwent resections at both metastatic sites. The primary CRCs were in 50% rectal and in 50% colonic carcinomas (61% node positive, all with free resection margins). Metastases occurred synchronously (regarding primary CRC) in 32% of the patients. In 86%, liver resection was performed prior to pulmonary resection. The first resection of metastases was performed a median of 16 months after resection of the primary CRC; the median interval between the first and the second resection of metastases was 7 months. Forty-seven percent of the patients also underwent at least a third metastasectomy. During resection of the first and second site of metastases, free margins were achieved in 98% and 95%, respectively. Survival analysis was performed using Kaplan–Meier and Cox regression methods. ResultsThe 5-year survival rates (SV) were 64% after initial surgery of CRC, 42% after the first resection of metastases, and 27% after the last metastasectomy. Patients with synchronous metastases had a 5-year SV after first metastasectomy of 43% and in patients with metachronous metastases of 41% (n.s.). The location of the primary tumor (20% 5-year SV in rectal vs. 57% in colonic cancer; p < 0.02) and the lung as primary site of metastatic disease (5-year SV 0% vs. 60% in patients with primarily hepatic metastases only; p < 0.001) significantly influenced survival in univariate analysis. Patients with rectal cancer had a significantly higher frequency of the lung as first metastatic site (46%) compared to patients with colonic cancer (14%; p < 0.03). Multivariate survival analysis revealed the lung as first metastatic site and as the sole significant independent factor for the outcome (p < 0.001; relative risk vs. liver first metastases 4.7). ConclusionIn selected patients with metastasized CRC resection of both hepatic and pulmonary metastases may improve survival rates or even provide long-term survival. Patients with lung as the first site of metastatic disease (either lung only or in combination with hepatic metastases) have a significantly worse outcome than patients with metastases primarily confined to the liver.

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models.

Surgical treatment of combined hepatic and pulmonary colorectal cancer metastases

Aims Surgical resection of combined hepatic and pulmonary metastases remains controversial in light of limited supportive evidence. This study aimed to audit our initial experience with this aggressive surgical strategy. Methods Between 1997 and 2006 we assessed 19 patients with colorectal cancer metastases for combined liver and lung metastasectomy, of whom 16 patients underwent surgery. We retrospectively reviewed perioperative and survival data. Results Synchronous liver metastases were present in three out of 16 patients at time of diagnosis of the primary tumour, and one out of 16 patients had synchronous lung and liver metastases with the primary tumour. Of those 12 patients who developed metachronous metastases five patients developed liver metastases first, one patient developed pulmonary metastases first, and six patients developed synchronous liver and lung metastases. Thirty nine operations were performed on 16 patients. The median hospital stay was 5.5 (2–10) days for the pulmonary and 7 (1–23) days for the hepatic resections. There were no in-hospital deaths. Chemotherapy was given to five patients prior to metastasectomy and nine received adjuvant chemotherapy following metastasectomy. Median survival from diagnosis of metastatic disease was 44 months (8–87 months). Estimated 1-year survival from diagnosis of metastatic disease was 94%, estimated 5-year survival was 20%. Conclusion We believe an aggressive but selective surgical approach to combined hepatic and pulmonary colorectal metastases is justified by limited resource requirements and encouraging survival.

Long-Term Survival After Repeated Resection of Pulmonary Metastases From Colorectal Cancer

The purpose of this study was to evaluate the outcome of patients undergoing repeated resection of pulmonary metastases from colorectal cancer and specify factors promising long-term survival. From January 1993 to December 2003, 175 patients were diagnosed and resected for pulmonary metastases of colorectal cancer. Follow-up information was collected for 169 patients, and 33 (19.5%) had had recurrent metastasectomies up to three times. Their follow-up information was updated in August 2006. The first repeated resection was performed for up to six bilateral metastases, the second and third metastasectomies were each unilateral and for a single metastasis only. Lymph node involvement was present in 5 patients who underwent repeat resections. The overall (n = 169) median survival was 47.2 months after the first metastasectomy. The 33 patients with repeated resections had a median survival of 72.6 months, with survival of 53.8% at 5 years and 20.6% at 10 years. After reoperation, age, sex, primary tumor stage, preoperative carcinoembryonic antigen, disease-free interval, prior resection of liver metastases, and lymph node involvement were not found to be of prognostic importance. The only factor that significantly influenced survival was the number of metastases (hazard risk, 1.299). Perioperative mortality even for repeated resections was 0%. Repeated resection of pulmonary metastases secondary to colorectal cancer is safe and can provide long-term survival for highly selected patients.

Multiple Resections for Hepatic and Pulmonary Metastases of Colorectal Carcinoma

Resections are effective for some patients with both hepatic and pulmonary metastases of colorectal cancer, but the best selection criteria for the resections and effective treatment for recurrence after the resections have not been determined. A retrospective analysis was performed for 30 consecutive patients who received aggressive multiple resections for both hepatic and pulmonary metastases of colorectal cancer. Recurrences after resections were surgically treated whenever resectable. For the 30 patients, 45 hepatectomies and 40 pulmonary resections were performed and 17 patients received three or more resections. No mortality was observed. Overall survival after the first metastasectomy for the second organ (liver or lung) was 58% and nine 5-year survivors were observed. Multivariate analyses revealed that primary colon cancer, stage IV in TNM classification and maximum size of hepatic tumor >3 cm at initial hepatectomy were poor prognostic factors, but several long-term survivors were observed even among patients with those factors. Multiple resections for hepatic and pulmonary metastases of colorectal cancer are safe and effective. No single factor is considered to be a contraindication for the resections. For recurrence after the resections, surgical resection is also recommended if resectable.

Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer

The purpose of this study was to identify the prognostic impact of unexpected lymph node metastases in patients undergoing resection of pulmonary metastases from colorectal cancer and specify the influence of pulmonary and mediastinal nodal involvement according to the modified Narukes lymph node mapping [Mountain CF, Dresler CM. Regional lymph node classification for lung cancer. Chest 1997;111(6):1718-23.]. From January 1993 to December 2003, 175 patients were diagnosed and resected for pulmonary metastases of colorectal cancer. Follow up informations were collected for 169 patients and an analysis of prognostic factors was performed. Ninety-six men (56.8%) and 73 women (43.2%) with a median age of 62 (range 34-81) were identified, 28 (16.7%) patients were found to have lymph node metastases, five of them were identified during a recurrent procedure. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of lymph node metastases on survival was analyzed with the log-rank test. Median survival was 47.2 months after first metastasectomy. Ten patients with intrapulmonary nodal involvement had a median survival of 86 months whereas 12 patients with hilar and six patients with mediastinal lymph node metastases had a median survival of 24.5 and 34.7 months. The survival difference between pulmonary and hilar/mediastinal metastases was statistically significant (p=0.008/p=0.07). Five year survival with pulmonary, hilar, and mediastinal metastases was 78.5, 0, and 0%, respectively. Perioperative mortality was 0%. Resection of pulmonary metastases secondary to colorectal cancer is safe and indicated in highly selected patients. Because tumor involvement of lymph nodes has a strong impact on survival; depending on their location, at least a lymph node sampling should always be performed. Adjuvant chemotherapy in case of proven lymph node metastases might be a good option to improve prognosis.