The role of pulmonary metastasectomy for pulmonary metastasis from head and neck cancer

The incidence rate of distant metastasis from head and neck (HN) cancers is 4.2–58.8%. The lung is the most common site of distant metastasis, and pulmonary metastasectomy (PM) can be performed in selected patients with pulmonary metastasis originating from HN cancers. However, due to the small number of study objectives, the knowledge on PM treatment of pulmonary metastasis from HN cancers remains insufficient, and the optimal management of pulmonary metastasis from HN cancer is unclear. Patients with pulmonary metastasis from HN cancer who underwent PM have a better prognosis than those who did not, with reported 5-year overall survival rates after PM of 20.9–59.4%. A histology of squamous cell carcinoma, incomplete resection, a short disease-free interval (DFI), and the oral cancer have been identified as factors predicting a worse prognosis after PM in this patient population. As a systemic therapy, longer overall survival has been achieved using immune check point inhibitors compared with standard single-agent therapies. Since the clinical and morphological diagnoses of pulmonary metastasis from HN cancers are often difficult, molecular techniques can provide useful information for the differential diagnosis between pulmonary metastasis from HN cancers and primary lung cancers. In cases of suspected pulmonary metastasis from HN cancer, the surgical strategy should be determined based on the patient’s clinical background.     

Pulmonary metastasectomy: limits to credibility

Lung metastases are a common site of spread for many malignant tumours. Pulmonary metastasectomy has been practiced for many years for sarcomas and is now becoming increasingly frequently advocated for patients with many other tumours, especially colorectal cancer. In this article we argue that this procedure is one framed by therapeutic opportunity and not supported by strong evidence. It is potentially harmful and may not be effective. Our argument is based on several important issues: (I) the vagueness of the concept of “oligometastases” and its biological implausibility; (II) the flaws in the often-cited observational evidence, especially selection bias; (III) the lack of any reliable randomised trial evidence of improved survival but evidence of harm; (IV) the failure of strategies to detect metastases earlier to influence overall survival. The introduction of stereotactic radiotherapy and image-guided thermal ablation have made the urge to treat lung metastases stronger but without any good evidence to justify their use. We acknowledge the problems of carrying out randomised trials when there is a clear lack of equipoise in the clinical teams involved but believe that there is an ethical need to do so. Many patients are probably being given false hope of cure or prolonged survival but are at risk of harm from pulmonary metastasectomy or ablation. It is possible that a few patients may benefit but without better evidence we do not know which, if any, do.     

Results of redo pulmonary metastasectomy

Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically analyze results of redo pulmonary metastasectomies. We reviewed a total of 3,523 papers. Among these, 2,019 were excluded for redundancy and 1,105 because they were not completely retrievable. Out of 399 eligible papers, 183 had missing information or missing abstract, while 96 lacked data on survival. A total of 120 papers dated from 1991 onwards were finally included. Data regarding mortality, major morbidity, prognostic factors and long-term survivals of the first redo pulmonary metastasectomies were retrieved and analyzed. Homogeneity of data was affected by the lack of guidelines for redo pulmonary metastasectomy and the risks of bias when comparing different studies has to be considered. According to the histology sub-types, redo metastasectomies papers were grouped as: colorectal (n=42), sarcomas (n=36), others (n=20) and all histologies (n=22); the total number of patients was 3,015. Data about chemotherapy were reported in half of the papers, whereas targeted or immunotherapy in 9. None of these associated therapies, except chemotherapy in two records, did significantly modify outcomes. Disease-free interval before the redo procedure was the prevailing prognostic factor and nearly all papers showed a significant correlation between patients’ comorbidities and prognosis. No perioperative mortality was reported, while perioperative major morbidity was overall quite low. Where available, overall survival after the first redo metastasectomy ranged from 10 to 72 months, with a 5-years survival of approximately 50%. The site of first recurrence after the redo procedure was mainly lung. Despite the data retrievable from literature are heterogeneous and confounding, we can state that redo lung metastasectomy is worthwhile when the lesions are resectable and the perioperative risk is low. At present, there are no “non-surgical” therapeutic options to replace redo pulmonary metastasectomies.     

History and present status of pulmonary metastasectomy in colorectal cancer

Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers, breast and lung, in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal. We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day. Our sources included published citation network analyses, the documented proposal for randomised trials, large systematic reviews, and meta-analysis of observational studies. The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done, or having been done, were not reported. Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias. Randomised controlled trials (RCTs) are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice. One such trial is recruiting and shows that controlled trial are possible.     

Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma： Analysis of prognostic factors

AIM： To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors.
METHODS： Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS： There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ＋ 28.2 （range： 1-99 mo）, and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma （HCC）, and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan Meier analysis revealed as a treatment for the that liver transplantation primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox＇s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC.
CONCLUSION： A metastasectomy should be performed before other treatments in selected patients, Although not significant, patients with liver transplantation of a primary HCC survived longer, Liver transplantation might be the most beneficial modality that can offer patients better survival, A multi- institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis.     

Preoperative evaluation and indications for pulmonary metastasectomy

Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.     

SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis

Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis–free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.The metastatic progression of breast cancer accounts for the majority of disease-related mortality. A major rate-limiting step in metastasis is the loss of function of the metastasis suppressor genes, which block a cascade of crucial steps including the loss of adhesion of primary tumor cells, intravasation into the blood and lymphatics with subsequent extravasation at distant sites, and the formation of new colonies. Despite the identification of the first metastasis suppressor gene, nonmetastatic 23 (NM23), nearly two decades ago (1), only a handful of new metastasis suppressors have been identified in recent years using candidate gene approaches (2, 3). It is likely that the current catalog of metastasis suppressor genes remains incomplete despite the vast sequencing efforts due to the possibility that a subset of genes regulated by epigenetic mechanisms may have eluded traditional discovery procedures (4–6). To identify these elusive metastasis suppressor genes, which are functionally compromised in late-stage disease (7–9), we took advantage of a well-established breast cancer progression cell line model system sharing the same genetic linage (Fig. 1A) (10). This model system consists of five cell lines that represent the various stages of breast cancer progression based on the MCF10A cell line: MCF10AneoT (NeoT), MCF10AT1Kcl2 (MII), MCF10CA1h (MIII), and MCF10CA1a (MIV). NeoT cells were generated by overexpression of HRAS in MCF10A cells and rarely exhibit growth following injection into nude mice. MII cells were generated by single xenograft passaging of NeoT cells. When injected subcutaneously (s.c.) into nude mice, MII cells generally form benign tumors that progress to carcinoma one out of four times; hence they mimic the early stage, carcinoma in situ. MIII and MIV cells were isolated from tumors formed by MII cells. MIII cells represent carcinoma, as in general they metastasize at a very low frequency, which requires a prolonged incubation period. On the other hand, MIV cells have the potential to readily seed lung metastases and represent the final stages of a breast cancer, metastatic carcinoma. We compared the gene expression profiles of these latter three model cell lines and leveraged large amounts of publically available breast tumor gene expression profiling data (11–13) by applying multiple bioinformatics filters to identify candidate metastasis suppressor genes.Open in a separate windowFig. 1.Identification of SDPR as a candidate metastasis suppressor gene. (A) Schematic depiction of the generation of breast cancer progression cell line model system. The model consists of five cell lines representing different stages of breast cancer progression. MI, normal breast epithelial cells; NeoT and MII, carcinoma in situ; MIII, carcinoma; and MIV, metastatic carcinoma. (B) Hierarchical clustering of gene expression profiles from MII, MIII, and MIV cells for the genes whose expression differ at least twofold between each cell line. Two clusters, cluster 6 and 7, are magnified because expressions of the genes in these two clusters are significantly suppressed in metastatic MIV cells compared with nonmetastatic MII and MIII. (C) The schematic summary of our strategy for the selection of SDPR as the top candidate metastasis suppressor.Here, we report the discovery of the phosphatidylserine-interacting protein, serum deprivation response (SDPR) (also known as cavin-2), as a bona fide metastasis suppressor. Thus far, studies on SDPR function have been limited to its role as a regulator of caveolae formation (14), and its potential direct involvement in cancer has not been previously described. However, it has been reported that SDPR expression is down-regulated significantly in not only breast cancer but also in cancers of kidney and prostate (15). Moreover, SDPR protein down-regulation was observed in serum from patients with malignant kidney tumors, and hence it was suggested as a possible diagnostic marker to discriminate malignant tumors from benign formations (16). Interestingly, SDPR is localized to 2q32-33, a region with a significant level of loss of heterozygosity that is associated with a high degree of recurrence in breast cancer (17, 18). Our results indicate that SDPR is capable of specifically inhibiting the metastatic growth of breast cancer cells.     

Nomogram for predicting distant metastasis of male breast cancer: A SEER population-based study

The main purpose of this study was to build a prediction model for male breast cancer (MBC) patients to predict the possibility of distant metastasis. The Surveillance, Epidemiology, and End Results database was used to obtain data on patients with MBC. The patients were divided into a training set and a validation set at a ratio of 7:3. The risk variables of distant metastasis in the training set were determined by univariate and multivariate logistic regression analyses. And then we integrated those risk factors to construct the nomogram. The prediction nomogram was further verified in the verification set. The discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve, calibration plots, respectively. A total of 1974 patients (1381 in training set and 593 in validation set) were eligible for final inclusion, of whom 149 (7.55%) had distant metastasis at the diagnosed time. Multivariate logistic regression analyses presented that age, T stage, N stage, and hormone receptor status were independent risk factors for distant metastasis at initial diagnosis of male breast cancer. Finally, the 4 variables were combined to construct the nomogram. The area under the curve values for the nomogram established in the training set and validation set were 0.8224 (95%CI: 0.7796–0.8652) and 0.8631 (95%CI: 0.7937–0.9326), suggesting that the nomogram had good predictive power. The calibration plots illustrated an acceptable correlation between the prediction by nomogram and the actual observation, as the calibration curve was closed to the diagonal bisector line. An easy-to-use nomogram, being proven to be with reliable discrimination ability and accuracy, was established to predict distant metastasis for male patients with breast cancer using the easily available risk factors.     

Pulmonary metastasectomy in soft tissue sarcomas: a systematic review

BackgroundSoft tissue sarcoma (STS) tend to metastasis to the lungs. Pulmonary metastasectomy seems to be a common practice always when plausible. The objective of this article was to review systematically the results of a literature search on pulmonary metastasectomy for STSs published in the last ten years and to offer a brief overview about the current practice as well.MethodsEight retrospective studies published in the period 2010–2020, which included patients with pulmonary metastases and metastasectomy were selected. Indication for surgery, survival rate and factors influencing survival were the primary outcomes, while further interesting findings in the studies were also collected and evaluated.ResultsCumulative 1,004 patients participated in these studies. The most common histological types were leiomyosarcoma, malignant fibrous histiocytoma (MFH) and synovial sarcoma, being present together at 60% of the study population. Five-year survival was reported to be in the range from 20–58%, better survival going along with a fewer (preferably one) metastases, longer disease free interval (DFI) and R0 resection in most of the cases.ConclusionsComplete resection of the metastatic lesions seems to be the most effective treatment for long-term survival, or even achieving cure in selected patients. At selection of the patients amenable for surgery, a high probability of R0 resection, as well as a disease free period of at least 12 months should perhaps bear a higher specific value.     

Tumour oxygenation: implications for breast cancer prognosis

There are areas of limited oxygen availability in most solid tumours, including breast cancer. Hypoxia in solid tumours is mainly a consequence of poor perfusion. Structural and functional abnormalities of newly formed tumour vessels cause spatial and temporal heterogeneity of tissue perfusion. The two principal mediators of hypoxia response, HIF‐1 and HIF‐2, are known to be stabilized at different oxygen levels and to have different temporal responses to hypoxia. Recently, stromal HIF‐1 and HIF‐2 have been suggested to have opposing roles in breast cancer progression. There is an established link between intralesional, severe hypoxia near areas of necrosis with high levels of HIF‐1 and poor prognosis in breast cancer. However, the biological effects of moderate hypoxia and the hypoxic response of stromal cells are currently topics of intense investigation.     

Risk factors and nursing countermeasures of postoperative pulmonary infection in patients with breast cancer: A retrospective analysis

It is necessary to elucidate the potential risk factors of pulmonary infection to provide references for the management of breast cancer.Our study was a retrospective design, patients who underwent modified radical mastectomy for breast cancer in our department of breast surgery from January 2019 to November 2020 were included. The personal and clinical data of included patients with and without pulmonary infection were compared.A total of 234 patients with radical mastectomy were included, the incidence of pulmonary infection was 15.38% with 95%confidence interval (CI) 11.42% to 18.98%. There were significant differences in the age, body mass index, diabetes, duration of surgery, combined radiotherapy and chemotherapy, and duration of drainage between patients with and without pulmonary infections (all P < .05). Logistic regression analysis indicated that age ≥55 years (odds ratio [OR] 2.128, 95%CI 1.105–3.426), body mass index ≥ 24 kg/m²(OR 2.344, 95%CI 1.031–3.299), diabetes (OR 2.835, 95%CI 1.132–4.552), duration of surgery ≥120 minutes (OR 1.394, 95%CI 1.012–1.044), combined radiotherapy and chemotherapy (OR 3.122, 95%CI 1.124–5.273), duration of drainage ≥5 days (OR 1.851, 95%CI 1.112–2.045) might be the independent risk factors of pulmonary infection in patients after radical mastectomy(all P < .05). Pseudomonas aeruginosa and Klebsiella pneumoniae are the most commonly seen bacteria.The incidence of postoperative pulmonary infections in breast cancer patients is high, and there are many associated risk factors. The perioperative management of patients should be strengthened targeted on those risk factors in clinical practice.     

Pulmonary metastasectomy for metachronous metastasis of esophageal cancer after esophagectomy

Background and objective

Pulmonary metastasectomy is a standard therapy for some types of metastatic lesions in the lung. Although the prognosis for esophageal cancer patients with pulmonary metastasis is poor, it has been reported that some post-esophagectomy patients have good prognosis after pulmonary metastasectomy. We investigated the role of resecting pulmonary metastases arising from esophageal cancer at our institution.

Patients and methods

Seven patients with primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who underwent resection of metachronous pulmonary metastases at our institution between 2006 and 2012 were identified from a retrospective database. All patients had undergone curative resection of their primary esophageal carcinoma.

Results

Six patients had unilateral and solitary lung metastasis. One patient presented with one metastatic lesion on each side, and he underwent 4 metastasectomy for pulmonary metastasis 3 times. There was no perioperative morbidity or mortality. The disease-free interval after esophagectomy ranged from 191 to 559 days (median, 463 days). Survival after pulmonary metastasectomy ranged from 357 to 3191 days (median, 1803 days). Three patients received systemic chemotherapy before metastasectomy. Currently, 5 patients are alive without evidence of recurrent disease.

Conclusion

Pulmonary metastasectomy may be acceptable as a part of multimodal treatment for solitary metachronous pulmonary metastasis in esophageal carcinoma.

     

Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

ObjectiveTo analyze breast cancer bone metastasis related gene-CXCR4.MethodsThis research screened breast cancer bone metastasis related genes by high-flux gene chip.ResultsIt was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis.ConclusionsThe bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.     

Diagnostic and prognostic factors,and two nomograms for endometrial cancer patients with bone metastasis: A large cohort retrospective study

Patients with endometrial cancer (EC) who develop bone metastasis (BM) always imply a poorer prognosis. However, reliable predictive models associated with BM from EC are currently limited.We retrospectively analyzed data on 54,077 patients diagnosed with primary EC in the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression analysis was used to determine independent predictors of BM from EC. Univariate and multivariate Cox regression analyses were used to determine independent prognostic factors for EC with BM. Based on independent predictors and prognostic factors, we constructed a diagnostic nomogram and prognostic nomogram separately. Besides, calibration curves, receiver operating characteristic curves, and decision curve analysis were used to evaluate the models.A total of 54,077 patients with EC from the Surveillance, Epidemiology, and End Results database were included in this study, 364 of whom had BM. Multivariate analysis in the logistic model showed that lung metastasis, liver metastasis, brain metastasis, N stage, T stage, histologic grade, and race were risk factors for BM from EC. Multivariate analysis in the Cox model showed that liver metastasis, brain metastasis, chemotherapy, surgery, and histologic type had a significant effect on overall survival. Moreover, the receiver operating characteristic curve, calibration curve, and decision curve analysis indicated the good performance of both diagnostic and prognostic nomograms.Two clinical prediction model was constructed and validated to predict individual risk and overall survival for EC with BM, respectively. Diagnostic nomogram and prognostic nomogram are complementary, improving the clinician''s ability to assess the patient''s prognosis and enhancing prognosis-based decision making.     

Lymph node metastasis in differentiated-type early gastric cancer: a single-center retrospective analysis of surgically resected cases

Background. Lymph node metastasis (LNM) from early gastric cancer (EGC) is rare, especially for differentiated-type EGC. However, LNM has been reported in a few cases after endoscopic curative resection of differentiated-type EGC. This study aimed to evaluate LNM risk factors to identify those that should be considered during the preoperative evaluation of differentiated-type EGC. Patients and methods. A total of 976 EGC patients who underwent radical gastrectomy were reviewed in this study. Univariate and multivariate analyses were used to analyze the predictive factors for LNM based on the histology of the differentiated-type EGC cases. Results. Differentiated-type EGC was observed in 59% of the cases. The rate of LNM was 6.6% (38/576 patients) in the differentiated-type EGC cases. Macroscopic shape, ulcers, tumor size, deeper invasion and lymphovascular invasion were shown to be related to LNM in differentiated-type EGC. Multivariate analysis revealed that size, depth, ulceration and lymphovascular invasion were independent predictors of LNM in differentiated-type EGC. When lymphovascular invasion was absent, the presence of one or more of the risk factors of ulcer lesions, tumor size >30 mm and submucosal invasion increased the rate of LNM. Thirteen patients who underwent radical gastrectomy were shown to have differentiated-type EGC with LNM that met the standard and expanded criteria of endoscopic submucosal dissection. Conclusions. As endoscopic resection is widely used, it is important to clarify the clinical significance of LNM in differentiated-type EGC and to screen for LNM with this incidence in mind and to follow the clinical courses of such cases, especially in China.     

Mesorectum localization as a special kind of rectal metastasis from breast cancer

Breast cancer can metastasize to other organs following initial treatment. Bones, liver, and the lung are the most common sites of breast cancer metastases. The digestive tract, on the other hand, is rarely involved. The incidence of mesorectal metastasis(a special category of rectal metastases) from breast cancer has not been described before. The case reported herein concerns a 68-year-old woman who underwent mastectomy. A pelvic mass with no symptoms was subsequently identified by computed tomography in the patient. We ultimately confirmed that this mass was a metastasis from breast cancer located in the mesorectum using surgical exploration and pathology results.     

Cardiac metastasis due to pulmonary metastasis from a transitional cell carcinoma

We report a rare case of symptomatic cardiac metastasis froma transitional cell carcinoma of the renal pelvis diagnosedby echocardiography. A 75-year-old patient with a long historyof neoplasm since 1999 and coronary artery disease with CABGin 2003, was admitted to our department. He underwent cardiacsurgery using cardiopulmonary bypass with tumor excision. Histologicallyit was the same type of transitional cell neoplasm which wasoperated seven years before. We present all medical history, detailed 2D and 3D echocardiography,intraoperative pictures and discuss possible chain of changesfrom renal pelvis cancer to clinical manifestation of cardiacmass. There is proved a rapid progression of cardiac tumor withclinical manifestation few months after control TEE examinationwithout any evidence of cardiac mass. It is important that thisis a very rare case of left heart metastasis from right sideof circulatory system through pulmonary stage of cancer progression.