Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases

BACKGROUND Evaluating the psychological resilience of lung cancer(LC)patients helps understand their mental state and guides future treatment.However,there is limited research on the psychological resilience of LC patients with bone me-tastases.AIM To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience.METHODS LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University.The psychological scores of the enrolled patients were collected.They were then grouped based on the mean psychological score:Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group.The baseline data(age,gender,education level,marital status,residence,monthly income,and religious beliefs),along with self-efficacy and medical coping mode scores,were compared.RESULTS This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023,with an average psychological resilience score of 63.24±9.96 points.After grouping,the low-score group consisted of 69 patients,including 42 males and 27 females,with an average age of 67.38±9.55 years.The high-score group consisted of 73 patients,including 49 males and 24 females,with a mean age of 61.97±5.00 years.χ2 analysis revealed significant differences between the two groups in education level(χ2=6.604,P=0.037),residence(χ2=12.950,P=0.002),monthly income(χ2=9.375,P=0.009),and medical coping modes(χ2=19.150,P=0.000).Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores(t=3.383,P=0.001)and lower age than the low-score group(t=4.256,P<0.001).Furthermore,multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience[odds ratio(OR)=0.926,P=0.035,95%confidence interval(CI):0.862-0.995],while age(OR=1.099,P=0.003,95%CI:1.034-1.169)and medical coping modes(avoidance vs confrontation:OR=3.767,P=0.012,95%CI:1.342-10.570;resignation vs confrontation:OR=5.687,P=0.001,95%CI:1.974-16.385)were identified as independent risk factors.A predictive model based on self-efficacy,age,and medical coping modes was developed.The receiver operating characteristic analysis showed an area under the curve value of 0.778(95%CI:0.701-0.856,P<0.001),indicating that the model has good predictive performance.CONCLUSION LC patients with bone metastases are less psychologically resilient than the general population.Factors such as self-efficacy,age,and medical coping modes influence their psychological resilience.Patients with low self-efficacy,old age,and avoidance/resignation coping modes should be closely observed.

Thymic carcinoid with multiple bone metastases:A case report

BACKGROUND Thymic carcinoid(TC)is a rare entity among anterior mediastinal malignancies.TCs are neuroendocrine carcinomas that constitute approximately 2%–5%of all thymic epithelial tumors.CASE SUMMARY The study reported a rare TC with multiple bone metastases.A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg.Magnetic resonance imaging scans revealed damage to the lumbar spine,sacrocaudal vertebrae and iliac crest,suggesting bone metastasis;computed tomography(CT)scan of the thorax showed a calcified anterior mediastinal mass;positron emission tomography-CT demonstrated multiple abnormal bone signals;and laboratory work-up showed no endocrine abnormalities.Fine-needle aspiration biopsy revealed predominantly single small,round to oval cells with scant cytoplasm and some loose clusters,suggesting endocrine manifestations.The pathological diagnosis was atypical carcinoid,which tend to originate from the thymus and was classified as intermediate-highly invasive.The patient underwent anlotinib-targeted therapy.Anlotinib(12 mg)was administered daily for 2 wk,after which the patient was allowed to rest for 21 d.Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29%after therapy.Treatment has a long stable disease benefit of more than 2.5 years.CONCLUSION These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.

U-Net Based Dual-Pooling Segmentation of Bone Metastases in Thoracic SPECT Bone Scintigrams

In order to enhance the performance of the CNN-based segmentation models for bone metastases, this study proposes a segmentation method that integrates dual-pooling, DAC, and RMP modules. The network consists of distinct feature encoding and decoding stages, with dual-pooling modules employed in encoding stages to maintain the background information needed for bone scintigrams diagnosis. Both the DAC and RMP modules are utilized in the bottleneck layer to address the multi-scale problem of metastatic lesions. Experimental evaluations on 306 clinical SPECT data have demonstrated that the proposed method showcases a substantial improvement in both DSC and Recall scores by 3.28% and 6.55% compared the baseline. Exhaustive case studies illustrate the superiority of the methodology.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

31inical features and prognostic factors for patients wilh bone metastases from prostate cancer

To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer （PCa）. We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009. The overall survival rate after bone metastases was calculated using the Kaplan-Meier method. The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models. The follow-up rate was 100%, the follow-up cases during 1, 3 and 5 years were 103, 79 and 55, respectively. The 1-, 3- and 5-year survival rates were 89.1%, 60.9% and 49.8%, respectively, with a median survival time of 48.5 months for patients with bone metastases from PCa. In univariate analysis, age, Gleason score, clinical stage, the number of bone lesions, alkaline phosphatase （ALP） level, invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis. By multivariate analysis using Cox regression, ALP level, Gleason score and non-regional lymph node metastases were independent prognostic factors. These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

Bone metastases from hepatocellular carcinoma:clinical features and prognostic factors

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

Bone metastases:When and how lung cancer interacts with bone

Bone metastasis is a common and debilitating consequence of lung cancer:30%-40% of patients with nonsmall cell lung cancer develop bone metastases during the course of their disease. Lung cancer cells find a favorable soil in the bone microenvironment due to factors released by the bone matrix, the immune system cells, and the same cancer cells. Many aspects of the cross-talk among lung tumor cells, the immune system,and bone cells are not clear, but this review aims to summarize the recent findings in this field, with particular attention to studies conducted to identify biomarkers for early detection of lung cancer bone metastases.

Targeting mast cells in gastric cancer with special reference to bone metastases

Bone metastases from gastric cancer(GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells(MCs) positive to tryptase(MCPT) in primary gastric tumor angiogenesis. Recently,we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating,peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents,such as MCs tryptase inhibitors(gabexate mesylate,nafamostat mesylate) or c-KitR tyrosine kinase inhibitors(imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patientsaffected by bone metastases.

Bone metastases as initial presentation of hepatocellular carcinoma

Extra-hepatic spread is present in 5% to 15% of patients with hepatocellular carcinoma(HCC) at the time of diagnosis. The most frequent sites are lung and regional lymph nodes. Here, we report 3 cases of unsuspected HCC with symptoms due to bone lesions as initial presentation. Morphological characteristics and immunohistochemistry from the examined bone were the key data for diagnosis. None of the patients had an already known chronic liver disease. Differential diagnoses with HCC upon ectopic liver disease or hepatoid adenocarcinoma were shown. Therapy with the orally active multikinase inhibitor sorafenib plus symptomatic treatment was indicated.

Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases.

The efficacy of ^(89)Sr combined with ^(99)Tc-MDP in the treatment of the advanced breast cancers with bone metastases

Objective： The aim of our study was to evaluate the efficacy of 89Sr combined with Technetium [^99Tc] Methylene- diphosphonate Injection （^99Tc-MDP） in the treatment of cancer pain in the advanced breast cancers with bone metastases. Methods： A total of 80 patients with various degrees of bone pain due to multiple metastases of breast cancer were treated with ^89Sr combined with ^99Tc-MDP. ^89Sr was given intravenously at 4mCi on day 1 during the 3-month schedule. After 7 days, ^99Tc-MDP was given at 22 rag/day on days 1-10 during the 1-month schedule, for 3 to 6 months. Results： The effective rate of relieving pain was 83.75%. The effective rate of curing bone metastases was 81.25%. So there was a significant improvement in the quality of life of the patients. Conclusion： ^89Sr combined with ^99Tc-MDP are effective in the treatment of cancer pain in the breast cancers with bone metastasis, and can obviously repair the bone destruction caused by metastases, thereby improving the quality of life in advanced breast cancer patients with bone metastases.

Role of TGF-<i>β</i>in breast cancer bone metastases

Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases.

Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment

While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.

Clinical application value of bone turnover markers in non-small-cell lung cancer patients with bone metastases

Objective:The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer(NSCLC) patients with bone metastases.Including diagnosing bone metastases,detecting bone metastatic spread.Methods:Alkaline phosphatase(AKP),β-C-terminal telopeptide of type I collagen(β-CTx),osteocalcin(OST) and bone alkaline phosphatase(BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people.Results:The level of AKP,β-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people.Significant correlation was observed among bone turnover markers.The levels of BALP and OST were significantly correlated with the extent of bone metastasis.The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture.Conclusion:In NSCLC patients with bone metastases,bone turnover markers can help to make diagnosis and evaluate the severity.It will have a wide range of use in clinical practice.

Lymph node,peritoneal and bone marrow micrometastases in gastric cancer:Their clinical significance

The 7th TNM classification clearly states that micro-metastases detected by morphological techniques(HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease(pN1mi or M1),while patients in whom micrometas-tases are detected by non-morphological techniques(e.g.,ow cytometry,reverse-transcriptase polymerase chain reaction) should still be classif ied as N0 or M0.In gastric cancer patients,micrometastases have been de-tected in lymph nodes,the peritoneal cavity and bone marrow.However,the clinical implications and/or their prognostic signif icance are still a matter of debate.Cur-rent literature suggests that lymph node micrometasta-ses should be encountered for the loco-regional staging of the disease,while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes.Peritoneal fluid cytology ex-amination should be obligatorily performed in pT3 or pT4 tumors.A positive cytology classif ies gastric cancer patients as stage Ⅳ.Although a curative resection is not precluded,these patients face an overall dismal prognosis.Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further.Gas-tric cancer cells are detected with high incidence in the bone marrow.However,the published results make comparison of data between groups almost impossible due to severe methodological problems.If these meth-odological problems are overcome in the future,specif ic target therapies may be designed for specif ic groups of patients.

Bone and brain metastases from ampullary adenocarcinoma

Ampullary carcinoma is the second most common cancer of the peri-ampullary area after pancreatic carcinoma and metastasizes mostly intra-abdominally and to the liver.Extra-abdominal metastases are less frequent.In this report we describe the case of a patient with resected adenocarcinoma of the ampulla of Vater who developed skeletal metastases in the lower extremity and brain metastases.We briefly discuss aspects of this comparatively rare gastrointestinal malignancy.