Changing metastatic patterns of osteosarcoma

The clinical courses of 111 patients with osteosarcoma treated at UCLA between 1971 and 1982 were reviewed to ascertain the evolution of the natural history of this disease. Only patients with classic high-grade intraosseous osteosarcoma of the extremity, scapula, or pelvis were considered. Patients with low-grade parosteal osteosarcomas; primary osteosarcomas of the face, skull, vertebra, or ribs; and osteosarcomas arising in Paget's disease or previously irradiated bones were not included. Fifty-nine patients developed clinically evident distant metastases. Of these, 36 developed pulmonary metastases alone as the initial site of recurrence. Eighteen of 19 (94.7%) patients treated between 1971 and 1974 by amputation alone developed pulmonary relapse as the initial site of recurrence, whereas only 18 of 40 patients (45%) treated after 1974 with surgery and adjuvant chemotherapy developed pulmonary metastases alone as the initial site of recurrence. Although no patients in the early group developed an extrapulmonary metastasis as the initial site of recurrence, 11 of 40 patients (27.5%) treated with adjuvant chemotherapy developed an extrapulmonary metastasis as the initial site of recurrent disease, and 11 patients developed simultaneous pulmonary and extrapulmonary metastases. Although it is impossible to attribute this alteration in metastatic pattern to adjuvant chemotherapy alone, it is apparent that nonpulmonary metastases are becoming more common among patients currently treated for osteosarcoma.     

Prognostic factors and imaging patterns of recurrent pulmonary nodules after thoracotomy in children with osteosarcoma

BACKGROUND: In children with osteosarcoma who have undergone thoracotomy, it often is difficult to distinguish metastatic from benign recurrent pulmonary nodules. The authors of this study sought to identify any computed tomography (CT) imaging pattern of recurrent pulmonary metastases in this patient population. The authors also sought to identify associated prognostic factors. METHODS: CT scans obtained after thoracotomy were available for 35 patients with osteosarcoma who had undergone resection of presumed pulmonary metastases at St. Jude Children's Research Hospital (Memphis, TN). CT scans obtained before the initial thoracotomy were available for 33 of the 35. The authors recorded location, histologic diagnosis, and time of development of the original pulmonary nodules, time of recurrence of pulmonary disease; the location of recurrent nodules, and the presence of calcification, adenopathy, or progressive pleural disease, as well as patient demographic data, survival data, and location of the primary tumor site. RESULTS: Pulmonary nodules recurred in 32 of the 35 patients after thoracotomy. Nineteen of these patients underwent resection of the recurrent lesions and 1 who died underwent an autopsy; 18 of the 20 patients had metastatic disease. The only CT finding consistently associated with recurrent metastatic disease was progressive pleural thickening, which predicted a poor outcome. The occurrence of a solitary pulmonary nodule in the lung contralateral to the previous surgery was associated almost always with a benign process. CONCLUSIONS: CT imaging cannot distinguish reliably between benign and metastatic recurrent pulmonary disease after thoracotomy in patients with osteosarcoma. Recurrent pulmonary disease in this set of patients is likely to be metastatic, and aggressive surgical intervention is probably warranted. In this study, patients who had progressive pleural disease after thoracotomy consistently experienced pulmonary metastatic recurrence and had a poor prognosis.     

Expression of variant CD44, exon 6 in patients with metastatic pulmonary tumor

High expression ratios of CD44 variant 6 (CD44 V6) in patients with metastatic pulmonary tumor were found in those with primary lesions of cancer of the colon, uterus, larynx, liver and osteosarcoma. It was clarified that patients showing expression of CD44 variant 6 likely revealed pulmonary metastasis at earlier time following operations of primary cancer (p<0.05). CD44 V6, an adhesion molecule, was a factor to participate in pulmonary metastases from various organ cancers. No significant correlation was observed in survival between patients with CD44 V6 positive versus negative tumors, except laryngeal tumor after resection of primary or metastatic lung tumor. CD44 V6 related to its invasive and further metastatic functions in metastatic lung tumor. We suggest that cancer cells expressing the CD44 molecule especially V6 may adhere to vascular endothelium and hyaluronic acid in the lung. And cancer cells without this molecule liberated from the primary focuses hardly adhere to the pulmonary tissues supposedly resulting in delayed metastases and proliferations in the pulmonary tissues.     

Estimation of the time of pulmonary metastasis in colorectal cancer patients with isolated synchronous liver metastasis

OBJECTIVE: The aim of this study was to estimate the time when pulmonary metastases began to grow in colorectal cancer (CRC) patients with isolated synchronous liver metastasis based on the tumor doubling time (DT). METHODS: We examined 23 pulmonary metastases in 14 patients detected after resection of liver metastases from CRC (group 1) and 19 pulmonary metastases in eight patients detected after initiation of hepatic arterial infusion chemotherapy for synchronous unresectable liver metastases (group 2). The regression line was determined from the chest X-ray films, and the DT was calculated. RESULTS: We estimated the DTs of pulmonary metastases as 65.0 +/- 28.9 and 76.2 +/- 23.0 days in groups 1 and 2, respectively, and the time when pulmonary metastases began to grow as 16-1418 and 112-1464 days before the resection of liver metastases for 19 lesions in 12 out of 14 patients of group 1 and before resection of primary CRC in group 2, respectively. CONCLUSION: It appears that in some CRC patients in whom the metastatic site is considered to be limited to the liver at diagnosis, occult pulmonary metastasis has already taken place.     

Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide

We report on the clinical course and outcome of 28 patients, treated at The Istituti Ortopedici Rizzoli between 1995 and 1997 for osteosarcoma of the extremities metastatic to the lung at presentation. The treatment for these patients was the following: primary chemotherapy with cisplatin, adriamycin and high dose of methotrexate and ifosfamide followed by simultaneous resection of primary and metastatic lesions (when feasible), and further chemotherapy. After primary chemotherapy, lung metastases disappeared in 6 patients, whereas metastases in 3 remained surgically unresectable. These 9 patients received surgical treatment of the primary tumor only. In the remaining 19 patients, after chemotherapy, a simultaneous resection of the primary and metastatic tumor was performed. The resection of metastatic lesions was complete in 18 cases and incomplete in one. Three of the 4 patients who did not achieve a tumor-free status died in a few months and one is still alive with uncontrolled disease. With a median follow-up of 32 months (19-43) of the 24 patients who achieved remission, 12 (55%) remained continuously free of disease, 11 relapsed with new metastases and 1 died of chemotherapy-related toxicity. The 2-year DFS and OS were 36% and 53% respectively. These results are much worse than those achieved in 114 contemporary patients with localised disease (2-year DFS: 81%) treated in the same period and they are superimposible to the results achieved in 23 patients previously treated with the same protocol, but with standard dose of ifosfamide (2-year DFS: 32%). However, it must be underlined that, as regards prognosis, patients with metastatic disease at presentation are a hetero-geneous group. The DFS was significantly higher for patients with only one or two metastatic lesions than for patients with 3 or more lesions (2 year DFS: 78% vs. 28%). In 12 of the 19 patients who had a complete simultaneous resection of the primary and metastatic tumor, a strong correlation between the degree of necrosis of the primary and metastatic lesions was found. We conclude that in patients with osteosarcoma of the extremity with lung metastases at presentation: a) the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic tumors works very well only for those patients who present with one or two metastatic nodules whereas for patients with 3 or more pulmonary metastases the prognosis is very poor; b) within the 4-drug regimen used in this study, the increment of ifosfamide dose from 10 g/m2 to 15 g/m2 for cycle does not improve prognosis; c) the strong correlation found between the histologic response of the primary tumor and metastases supports the strategy, largely used nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemo-therapy on the basis of the primary tumor histologic response to preoperative chemotherapy.     

宫颈癌肺转移患者手术治疗效果及预后因素分析

目的:通过对宫颈癌治疗后肺转移患者临床资料进行分析,评价外科手术治疗宫颈癌肺转移的疗效,研究影响患者生存的预后因素.方法:回顾性分析44例宫颈癌治疗后肺转移患者临床资料(手术组23例,对照组21例),采用Kaplan-Meier法进行生存分析,Log-rank检验进行单因素分析,COX风险回归模型进行多因素分析.结果:手术组1、2年生存率分别为78.2%、34.7%.手术组患者的生存曲线高于非手术组患者的生存曲线,差异有统计学意义(P<0.05),单因素分析显示,肿瘤分化程度、肺转移瘤数目、肺转移性肿瘤最大直径与患者生存率有关(P<0.05);COX比例风险回归模型分析显示,肺转移瘤数目及肺转移肿瘤最大直径是宫颈癌肺转移患者预后的独立影响因素(P<0.05).结论:对于肺转移灶数目较少,直径较小的患者,可从肺转移灶切除中获益,积极行肺转移瘤外科治疗有助于改善宫颈癌肺转移患者的长期预后.     

Surgical resection of pulmonary metastases from colorectal cancer. 10-year follow-up

Pulmonary resection of metastatic lesions from colorectal cancer was performed in 62 patients, and their cumulative 5-year and 10-year survival rates were 42% and 22%, respectively. The overall median survival was 24 months. The survival curve decrease even after 5 years after pulmonary resection; four of 13 patients who survived more than 5 years subsequently died of metastatic disease and only two patients survived more than 10 years. The number and size of the pulmonary metastases were significantly correlated with postthoracotomy survival. Solitary metastases less than 3.0 cm in diameter were good indicators of favorable postthoracotomy survival. There were no significant differences in survival based on Dukes' classification or location of the primary lesion. Sex, age, disease-free interval between the primary tumor and appearance of metastasis, and extent of pulmonary resection had no influence on survival. It is impossible to say from our experience that surgical resection of pulmonary metastases increased the cure rate. Presumably a good 5-year survival rate after thoracotomy would be a reflection of a length bias caused by the biologic behavior of the metastatic pulmonary lesions.     

Loss of ErbB2 expression in pulmonary metastatic lesions in osteosarcoma.

OBJECTIVES: The c-erbB2 protooncogene is located on human chromosome 17 and encodes a 185-kilodalton transmembrane glycoprotein (ErbB2). Elevated ErbB2 expression or gene amplification has been shown to be associated with a poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of the ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. To further investigate the role of ErbB2 overexpression in pulmonary metastasis of osteosarcoma, its expression in the primary and metastatic lesions of the same osteosarcoma patients was compared. METHODS: We compared the expression levels of ErbB2 receptor protein between the biopsy samples and pulmonary metastatic lesions in each of 19 patients with osteosarcoma who had not presented with metastasis at diagnosis. All archival materials from patients were retrieved and stained with monoclonal antibody CB11 to detect ErbB2 protein. RESULTS: The rate of overexpression was significantly lower in the pulmonary metastatic tumors than in the biopsy samples (11 versus 42%; p = 0.03). Among 8 patients who had shown increased levels of ErbB2 in the biopsy samples, 7 exhibited complete absence of ErbB2 in the pulmonary metastatic lesions. Overall loss of ErbB2 expression was noted in 14 of 19 patients as the initial tumor became metastatic. CONCLUSIONS: It is suggested that overexpression of ErbB2 decreases within individual osteosarcomas as they become metastatic. Overexpression of ErbB2 may not play an important role in the development of pulmonary metastases of osteosarcoma. Further data are needed before ErbB2 can be used in making clinical decisions for osteosarcoma patients.     

A successful case of systemic chemotherapy followed by liver resection for advanced hepatocellular carcinoma with highly vascular invasion and multiple pulmonary metastases

The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.     

Hepatocellular carcinoma presenting with bone metastasis

Bone metastasis is an unusual complication of hepatocellular carcinoma. We report here 2 cases of patients with bone metastases of hepatocellular carcinoma at presentation. Patient No. 1 with liver cirrhosis and hepatocellular carcinoma was admitted with a bone metastasis in the rib. The patient was treated with hepatic arterial chemotherapy and rib resection. Patient No.2 was known to have an asymptomatic liver mass of uncertain histology for a year when he presented with back pain. Because of signs of spinal compression, laminectomy was performed, and the diagnosis of metastatic hepatocellular carcinoma was established. The presence of bone metastases in hepatocellular carcinoma at presentation is extremely rare. More frequently, bone lesions are observed after successful treatment of the primary liver tumor. Both surgery and radiotherapy are used as palliative treatment in bone metastases of hepatocellular carcinoma. The treatment of hepatocellular carcinoma presenting with bone metastasis by bone resection and intraarterial chemotherapy seems to be of limited impact on patient survival because of dissemination of micrometastases in other organs and the frequent presence of other comorbid conditions. However, effective palliation using this multimodality approach is feasible. Hepatocellular carcinoma should be considered in the differential diagnosis of bone metastases.     

Metastatic patterns of extremity myxoid liposarcoma and their outcome

BACKGROUND AND OBJECTIVES: Extremity myxoid liposarcomas have a unique extrapulmonary metastatic potential. We studied the metastatic pattern of extremity liposarcomas to determine what types of posttreatment imaging may be of value in the follow-up these patients. METHODS: Twenty-two patients from a total of 128 patients with primary extremity liposarcoma were treated at a tertiary care institution for subsequent metastases from January 1981 to January 2000. Median follow-up was 45 months (range: 6-270 months). Data on these patients was prospectively collected and then retrospectively analyzed for effect of metastatic pattern and treatment on outcome. RESULTS: Of these 22 patients, extrapulmonary metastases developed in 10, combined pulmonary and extrapulmonary metastases developed in 6, and isolated pulmonary metastases developed in 6. Of the 16 patients with extrapulmonary metastases, 13 were of the myxoid subtype. Of the 49 patients with extremity myxoid liposarcomas, metastases developed in 14 (29%). The most common sites of metastases among these 14 patients include: the retroperitoneum, 10 patients (71)%; intra-abdominal extra-hepatic, 7 patients (50%); spinal/paraspinal, 6 patients (43%). Only 3 of the patients are alive and disease free and all 3 of these patients are from the subgroup of 10 patients with only extra-pulmonary metastases (2 intra-abdominal and 1 retroperitoneal). CONCLUSIONS: Extremity myxoid liposarcomas have an unusually high predilection for extra-pulmonary metastases, frequently without any pulmonary metastases. After treatment of the primary tumor, these patients should be followed with periodic chest X-ray and abdominal/pelvic computed tomography (CT) scans. Any back or neurologic complaints should prompt additional imaging of the appropriate spinal area. Consideration should be given to surgical and adjuvant treatment of metastatic disease when appropriate.     

CT导向下原发性肝癌肺转移瘤内注射无水乙醇的疗效评价

背景与目的:肺是肝癌肝外转移最常见的器官,对于原发灶控制稳定而仅有肺转移瘤的肝癌患者,转移瘤的治疗效果就成为决定预后的关键因素.本研究通过CT导向下无水乙醇瘤内注射治疗原发性肝癌肺转移瘤的疗效评估其临床价值.方法:2004年8月至2006年9月,在CT导向下对17例原发性肝癌术后或原发性肝癌TACE术后原发灶控制稳定的肺转移瘤患者的37个肺转移灶行经皮经肺瘤内无水乙醇注射治疗,8周后复查胸腹部CT评估其临床疗效.结果:胸腹部CT复查显示.37个肺内转移灶中31个病灶无增大,增强扫描病灶无强化,其中26个病灶瘤内无水乙醇沉积完全,5个病灶沉积良好;6个病灶复查见肿瘤增大或无水乙醇明显流失,增强后有明显强化.所有患者肝内未见复发或原发灶仍维持稳定.术后8周疗效评价有效率达到83.8%,1年生存率64.2%,有7例患者至今仍生存,最长者生存超过2年.仅2例患者术中发生气胸,肺压缩均在30%以内,经施行气胸引流后3天肺组织就完全复张,未发生其他并发症.结论:CT导向下无水乙醇瘤内注射治疗肝癌肺转移瘤刨伤小、疗效确切、并发症少,值得临床推广应用.     

Metastatic osteosarcoma to lung: a clinicopathologic study of surgical biopsies and resections.

Metastatic tumor to the lungs is one of the most important factors in the poor prognosis of primary osteosarcoma of bone. Until recently, pulmonary resection alone was the only therapeutic method available to salvage these patients. Previous investigators have reviewed a number of clinical and pathologic parameters which may possibly relate to the prognosis of osteosarcoma and the occurrence of pulmonary metastases. The pathologic features of these latter lesions have received little attention other than to state that they generally are less differentiated than the primary tumor. A review of multiple pulmonary nodules resected from 15 patients has demonstrated that 66% of all lesions were essentially identical to the primary tumor. The 5-year survival from the original amputation was 33% in this series; however, it was not possible to prognosticate a favorable outcome from the metastasis, a similar type of observation which has been made by others in relation to the primary osteosarcoma.     

Intraoperative hyperthermic tissue ablation in pulmonary metastases: a case report

AIMS AND BACKGROUND: The surgical removal of lung metastases is controversial: some authors have reported good results in terms of prognosis and disease-free interval in patients affected by multiple metastases. Recently, percutaneous hyperthermic tissue ablation (HTA) has been used under CT guidance in solitary peripheral pulmonary tumors attached or close to the parietal pleura. METHODS AND STUDY DESIGN: We report the first intraoperative HTA of a lung metastasis from colorectal carcinoma, which might pave the way for possible future application of the procedure in patients with multiple pulmonary metastases. A 64-year-old patient affected by a rectal cancer was treated by abdominal perineal amputation followed by two lines of chemotherapy. After two years two lesions appeared in the lower left pulmonary lobe and another in the lower right lobe. The patient was monitored by three-monthly thoracic and abdominal CT. The lesions were stable for one year, but in the last two months one of the suspected metastases in the left lung increased from 1 to 2 cm. This was an indication for surgical removal. A mini posterolateral thoracotomy was performed. Thanks to complete collapse of the lung with manual squeezing of the parenchyma, ultrasonography provided satisfactory visualization of the two lesions. A frozen biopsy of the larger lesion was obtained which confirmed its metastatic nature. Ultrasound-guided HTA of the larger metastasis (2 cm) was performed. Final US demonstrated the change in the metastatic pattern. The two lesions were eventually removed by wedge resection using a TA 90 stapler. Histological examination of the two lesions confirmed the coagulative necrosis of the treated metastasis. No morbidity or pulmonary problems were recorded.     

Three-time resection of the rib metastasis from hepatocellular carcinoma after two hepatic resections--a case report

A 40s woman, who had undergone hepatic resection twice for hepatocellular carcinoma (HCC), was admitted to our hospital because of a tumor with pain on the right 9th rib. From the findings of chest computed tomography (CT), abdominal CT and bone scintigraphy, we diagnosed the rib metastasis of HCC without any other recurrences. Local resection of the right 9th rib was performed in July 2008. Histologically, the tumor of the rib was diagnosed as the metastasis of HCC. The patient's pain on the right rib was disappeared after the operation. After the rib resection, the recurrence of the remnant of the right 9th rib occurred in June 2009. Local resection of the rib was performed in July 2009. Afterward, the recurrence of the remnant of the right 9th rib occurred again in April 2010. Local resection of the tumor of the same rib was performed in May 2010. The patient is still alive five years after the first hepatectomy. For HCC patients whose intrahepatic lesion or other metastatic lesions are controllable and the metastatic bone lesion is solitary and easily resectable, a resection for bone metastasis from HCC is thus locally effective in patient's pain control.     

Response of DNA ploidy to chemotherapy in primary and metastatic lesions in human osteosarcomas.

Primary and pulmonary metastatic and pulmonary metastatic tumors (two synchronous and seven metachronous metastases) in nine patients with osteosarcomas were studied by DNA cytofluorometry. All patients were treated with both pre and postoperative chemotherapy. The results showed that all five diploid osteosarcomas and three of the four aneuploid tumors did not markedly change their ploidy pattern after preoperative chemotherapy, and had almost the same ploidy patterns as the pulmonary metastatic lesions. Those eight tumors showed poor histologic response and chemoresistance by the doxorubicin binding assay. Only one aneuploid osteosarcoma showing good histologic response and chemosensitivity changed its ploidy pattern to diploid, with the disappearance of aneuploid tumor cells and its synchronous pulmonary metastatic tumor also showed conversion to a diploid pattern with massive tumor necrosis. It is evident that those tumors showing no change in their ploidy pattern after chemotherapy were resistant to the chemotherapy. Therefore, we conclude that regardless of whether the pulmonary metastatic tumors were synchronous or metachronous, they showed the same change in their ploidy pattern as well as their chemosensitivity as the primary human osteosarcoma from which they were derived.     

P53 mutations in primary tumors and subsequent liver metastases are related to survival in patients with colorectal carcinoma who undergo liver resection

BACKGROUND: The appearance of p53 mutations in colorectal carcinoma was determined, independent of differentiation and tumor stage of the primary tumors, in relation to the survival of patients who were scheduled to undergo liver resection. METHODS: Tumor material was analyzed for p53 mutations in primary colorectal tumors and subsequent liver metastases from 41 consecutive patients who were scheduled to undergo surgical liver resection. DNA sequencing and immunohistochemical staining of p53 protein within tumor nuclei were performed. RESULTS: Primary tumors displayed p53 mutations within exons 5-9 in 41% of patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of metastatic lesions had the same single mutation that was found in the primary tumor, whereas 11% of metastatic lesions had one additional mutation within exons 5-9; 22% had mutations only in their liver metastases, whereas corresponding primary tumors displayed wild-type p53. None of the patients had mutated p53 in their primary tumor and wild type in their metastases. Survival after undergoing liver resection was correlated negatively (P < 0.05-0.01) with Duke Stages A-D classification of the primary tumors, tumor differentiation, and radicality (> 0.7-0.8 mm) of resected liver metastases. CONCLUSIONS: The presence of p53 mutations in patients with metastatic lesions was related significantly (P < 0.003) to better survival after the patients underwent liver resection compared with patients with wild type p53 in their metastatic lesions. This finding was not related to covariates, such as Duke classification, tumor differentiation, type of liver metastasis, or metastatic radicality during resections. Explanations for this unexpected finding remain unclear, although the authors speculate that occult tumor cells with p53 mutations may be less responsive to growth factor(s) exposure during hepatic regeneration after resection.     

Murine osteosarcoma primary tumour growth and metastatic progression is maintained after marked suppression of serum insulin‐like growth factor I

The insulin‐like growth factor I (IGF‐I) signaling pathway has been shown to play an important role in several aspects of cancer biology, including metastasis. The aim of this study was to define the contribution of serum (endocrine) and local (tumour microenvironment) IGF‐I on osteosarcoma tumour growth and metastasis, a cancer that is known to be dependent on the IGF‐I axis. To test this hypothesis, we evaluated the primary tumour growth and metastatic progression of K7M2 murine osteosarcoma cells injected to a genetically engineered mouse [liver‐specific IGF‐I deficient (LID)] in which serum IGF‐I levels are reduced by 75%, while maintaining expression of IGF‐I in normal tissues. We first demonstrated that IGF‐I in the tumour and the tumour‐microenvironment were maintained in the LID mice. Within this designed model, there was no difference in primary tumour growth or in pulmonary metastasis in LID mice compared to control mice. Furthermore, there was no difference in the number or localization of single metastatic cells immediately after their arrival in the lungs of LID mice and control mice, as analysed by single cell video microscopy. Collectively, these data suggest that marked reduction in serum IGF‐I is not sufficient to slow the progression of either primary or metastatic models of osteosarcoma. © 2008 Wiley‐Liss, Inc.     

Differential Diagnoses of Solitary Pulmonary Nodules in Patients with an Extrathoracic Malignant Tumor:CT and Parthologic Correlations

OBJECTIVE To determine the possibility of definitive diagnosis for solitary pulmonary nodules in patients with a primary extrathoracic malignant neoplasm (ETM-SPN), and to further evaluate the value of CT for differential diagnosis in ETM-SPN by a multivariate retrospective study.METHODS Eighty-three patients with pathologically and clinically proven ETM-SPN with a diameter smaller than 3 cm were included in this study.The pathological characteristics of the SPN were correlated with those of the extrathoracic neoplasm, with the patient's age, gender, smoking history, disease-free time interval between the diagnosis of the extrathoracic malignancy and that of the lung lesion. In all 83 cases, CT scans were reviewed to confirm the solitary nature, size, and nodular morphology of the lung lesion.RESULTS Of all 83 cases, the mean age was (57.43±15.34) years. There were 51 males and 32 females, with the ratio of 1.59:1. The lesions included solitary metastasis in 43 cases, pulmonary malignant lesions in 33, and benign lesions in seven. Between the primary lung cancers and solitary metastasis groups, there was no significant difference in the gender ratio (1.20:1 vs 2.31:1, x2=0.0209, P>0.05), but there was a significant difference between the mean age (62.48±11.96 years vs 54.10±16.49 years, t=3.34, P<0.05). in the primary lung cancer and metastasis patient group, the percentage of patients who had a smoking history were 39.3 %(11/17) and 35.9 %(14/39), respectively. Patients with a primary lung cancer had no significant higher frequency of smoking history than did those with a metastatic lesion (x2=0.640, P>0.05). Of 81cases who were followed-up, the mean time of the disease-free interval between extrapulmonary malignancy diagnosis and pulmonary lesion differentiation was 39.73± 6.29 months (range 0～300 months, median 20.00 months), whereas those in the primary lung cancer group and metastatic group were 65.62 ±13.45 months and 22.83 ±4.19 months respectively. This difference was significant between the two groups (Wilcoxon rank sum test, U=2.796, P<0.01). Of all 83 cases, there were ten extrapulmonary squamous carcinomas and 58 adenocarcinomas with ratio of primary lung cancer and solitary metastasis of the tumors were 7:3 and 24:34, respectively (x2 =1.781, P >0.05), without showing a statistically significant relevance between the pathologic patterns of extrapulmonary malignancy and characteristics of the lung nodules. Of all the 83 cases, the mean diameters were (2.77±1.25) cm, whereas the diameters of 33 cases of primary lung cancer and 43 cases of a solitary metastatic lesion were (2.86±1.18) cm and (2.62±1.31)cm, respectively. There was no association between the two groups (t=1.29, P>0.05). There was a statistically significant association between primary lung cancer and the metastatic group with spiculate and smooth edges of the lung lesion (x2=8.562, P<0.01; x2=15.220, P<0.001).The study showed that a lung nodule with a spiculatedmargin correlated with a primary lung carcinoma,whereas those nodules with a smooth edge may more frequently show as a metastastic pulmonary lesion. CT-pathologic correlative analyses of hilar and mediastinal adenopathy were reviewed in 37 patients who underwent Iobectomy and thoracotomy. There was no statistical significant difference between the primary lung cancer group and the metastatic group (x2=2.801,P>0.05).CONCLUSION The likelihood of a primary lung cancer versus a metastasis of ETM-SPN smaller than 3 cm mainly depends on the patient's age, free interval between the two tumors and CT morphological characteristics of the lung lesion. This study showed there was no significant relevancy to factors such as gender, smoking history, pathological patterns of the extrapulmonary neoplasm or whether there has hilar or mediastinal adenopathy.     

A case of synchronous hepatic and multiple pulmonary metastases from rectal cancer responding completely to UFT therapy after resection of primary and hepatic lesions

We report a case of disease-free survival with uracil-tegafur(UFT)therapy after resection of primary and hepatic lesions from rectal cancer. A 64-year-old female had synchronous hepatic and multiple pulmonary metastases from rectal cancer. Image studies including colonoscopy, CT, MRI and PET-CT showed 2 metastases of lung(rt. middle lobe and lt. upper lobe) and a metastasis of liver(S6)in addition to rectal cancer(Rb, pSM, pN1, ly2, v1). Abdominoperineal resection+D3 of rectal cancer was performed, followed by chemotherapy with UFT for 28 days, and then partial resection of liver. Resected specimens of the liver demonstrated a histological Grade 2 with many CD3-positive lymphocytes. After surgeries, chemotherapy with UFT was continued, resulting in a CR for pulmonary metastases. The patient has been well without any sign of recurrence 5 years after first surgery. This case indicated that UFT was effective for hepatic and pulmonary metastases from rectal cancer, partially due to T cells(CD3+)infiltrating the metastases.