Multiple Bone Metastases Research Articles

Retrospective analysis of risk factors for bone metastasis in newly diagnosed prostate cancer patients.

The aim of the study was to analyze the clinical data of newly diagnosed prostate cancer (PCa) patients with bone metastasis and to explore the relevant risk factors. The clinical data of 251 patients with PCa, who were initially diagnosed in our hospital from February 2015 to October 2021, were retrospectively analyzed. According to the whole-body bone scan results, patients were divided into the bone metastasis group (n = 66) and the non-bone metastasis group (n = 185). The patient's age, total prostate-specific antigen (TPSA), free PSA (fPSA), prostate volume, alkaline phosphatase (ALP), Gleason score, erythrocyte sedimentation rate (ESR), and pelvic lymph node metastasis were collected. Univariate correlation and multivariate regression analyses, together with receiver operating characteristic curve, were used to analyze PCa bone metastasis-related factors. The incidence of bone metastasis in newly diagnosed PCa was about 26.29% (66/251). Among them, the incidence of pelvic metastasis was the highest, at 78.78% (52/251), and multiple bone metastases were significantly higher than single bone metastasis (80.31% vs. 19.69%). Univariate correlation analysis indicated that age, Gleason score, ESR, TPSA, ALP, fPSA/PSA, capsular infiltration, and pelvic lymph node metastasis (p < 0.05) were highly correlated with PCa bone metastasis. Multivariate Logistic regression analysis showed that TPSA (95% CI: 0.977-1.284, p = 0.007), ALP (95% CI: 1.008-1.080, p = 0.016), Gleasons core (95% CI: 2.110-82.349, p = 0.006), ESR (95% CI: 1.062-1.104, p = 0.003), and pelvic lymph node metastasis (95% CI: 1.537--33.239, p = 0.012) were independent risk factors for bone metastasis of PCa. The cut-off values for TPSA, ALP, Gleason score, and ESR were 33.78 ng/ml, 73.65 U/L, 7.5, and 23.5 mm/h, respectively. Additionally, the respective sensitivities for TPSA, ALP, Gleason score, and ESR were 81.8%, 75.8%, 68.2% and 77.3%, and the respective specificities was 90.3%, 98.9%, 98.4%, and 74.6%. TPSA, ALP, Gleason score, ESR and pelvic lymph node metastasis are independent risk factors for bone metastasis of PCa.

Hypocalcemia After the Administration of Denosumab in a Patient With Osteoporotic Fracture and Vitamin D Deficiency

Denosumab is a potent antiresorptive agent used for the treatment of osteoporosis and the prevention of skeletal-related events in patients with multiple myeloma or bone metastasis from solid tumors. Although denosumab generally seems to be safe and well tolerated, denosumab-associated hypocalcemia may occur, and the majority of cases are asymptomatic or mild. Underlying malignancy, renal failure, calcium or vitamin D deficiency, and high bone turnover have been reported as risk factors for hypocalcemia. Here, the author reports a case of hypocalcemia and hypophosphatemia following the administration of denosumab for the treatment of osteoporotic fracture in a patient with underlying but unrecognized severe vitamin D deficiency. Following the supplementation of calcium, vitamin D, and phosphorus, serum calcium and phosphorus levels returned to normal levels after about 2 weeks. To avoid denosumab-associated hypocalcemia, calcium and vitamin D status, as well as renal function should be assessed and corrected if appropriate. J Endocrinol Metab. 2022;12(3):111-115 doi: https://doi.org/10.14740/jem810

Application of 18F-FDG PET-CT Images Based Radiomics in Identifying Vertebral Multiple Myeloma and Bone Metastases.

PurposeThe purpose of this study was to explore the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) image radiomics in the identification of spine multiple myeloma (MM) and bone metastasis (BM), and whether this method could improve the classification diagnosis performance compared with traditional methods.MethodsThis retrospective study collected a total of 184 lesions from 131 patients between January 2017 and January 2021. All images were visually evaluated independently by two physicians with 20 years of experience through the double-blind method, while the maximum standardized uptake value (SUVmax) of each lesion was recorded. A total of 279 radiomics features were extracted from the region of interest (ROI) of CT and PET images of each lesion separately by manual method. After the reliability test, the least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation were used to perform dimensionality reduction and screening of features. Two classification models of CT and PET were derived from CT images and PET images, respectively and constructed using the multivariate logistic regression algorithm. In addition, the ComModel was constructed by combining the PET model and the conventional parameter SUVmax. The performance of the three classification diagnostic models, as well as the human experts and SUVmax, were evaluated and compared, respectively.ResultsA total of 8 and 10 features were selected from CT and PET images for the construction of radiomics models, respectively. Satisfactory performance of the three radiomics models was achieved in both the training and the validation groups (Training: AUC: CT: 0.909, PET: 0.949, ComModel: 0.973; Validation: AUC: CT: 0.897, PET: 0.929, ComModel: 0.948). Moreover, the PET model and ComModel showed significant improvement in diagnostic performance between the two groups compared to the human expert (Training: P = 0.01 and P = 0.001; Validation: P = 0.018 and P = 0.033), and no statistical difference was observed between the CT model and human experts (P = 0.187 and P = 0.229, respectively).ConclusionThe radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax.

Outcomes and prognostic factors after surgery for bone metastases in the extremities and pelvis: A retrospective analysis of 140 patients

BackgroundSurgical therapy of bone metastases is becoming increasingly important due to prolonged life expectancy and improved oncological treatment options. In a mostly palliative approach, it is necessary to identify those patients who might benefit from surgery. The shorter the remaining lifetime, the more restricted the indication and the less radical the intervention should be. The aim of this study was to evaluate the postoperative outcomes and prognostic factors for survival of patients with surgically treated bone metastases. MethodsWe retrospectively included 140 patients who underwent surgery for 151 bone metastases in the extremities and pelvis at our hospital between 2010 and 2020. We examined patient demographics, surgical procedures, 30-day complications, local tumour progression, and reoperations. Survival was calculated using Kaplan-Meier analysis. Prognostic factors were investigated by univariate analysis using the log-rank test and multivariate analysis using the Cox regression hazard model. ResultsIn 138 patients, the median survival time was 12.3 months. The overall survival rates at one, two, three and five years were 52.3%, 37.6%, 28.0%, and 18.0%, respectively. In univariate analysis, lung cancer, renal cell carcinoma, pathological fracture, visceral metastasis and multiple bone metastases were significantly associated with prognosis. No significant influence was determined for gender, age, location of bone metastasis, type of surgical procedure and time between diagnosis of primary tumour and surgery for bone metastasis. Multivariate analysis confirmed that pathological fracture, visceral metastasis and lung cancer were negative prognostic variables in terms of survival. Within 30 days, the incidence of complications was 25.0% and mortality was 9.3%. The most common complications were urinary tract infections (5.0%), pneumonia (4.3%), and delirium (2.9%). Local tumour progression occurred in 12 patients (8.7%) and five reoperations (3.6%) were performed. There were no significant differences between patients treated with endoprosthetic replacement (n = 47) and those treated with internal fixation (n = 91) in terms of 30-day complications and mortality as well as local tumour progression. ConclusionsSurvival of patients after surgery for bone metastases in the extremities or pelvis is very limited. The presence of a pathological fracture, visceral metastasis and lung cancer were independent prognostic factors for poor survival. Both internal fixation and endoprosthetic replacement achieved similar outcomes.

Case Report: Metastatic Signet-Ring-Cell Carcinoma of the Bladder From Breast Invasive Lobular Carcinoma Detected by Computed Tomography

Secondary bladder tumors are relatively rare among all bladder tumors, while bladder metastases from breast cancer have been rarely reported. Furthermore, signet-ring differentiation may appear in the metastases from a breast invasive lobular carcinoma regardless of whether the primary breast tumor had signet-ring cells, which may cause diagnostic uncertainty. We report a case of a 55-year-old female patient with diffuse bladder thickening as the chief complaint and no specific clinical manifestations. While the cystoscopy showed multiple scattered red protuberances, the biopsy suggested signet-ring-cell carcinoma. The gastroscopy results suggested poorly differentiated adenocarcinoma with signet-ring cells. Considering the patient’s history of invasive lobular carcinoma of the breast, chronic myeloid leukemia, and metastatic endometrial carcinoma from the breast, we performed an immunohistochemical analysis and the results indicated that signet-ring-cell carcinomas of the stomach and bladder originated from the invasive lobular carcinoma of the breast. We performed positron emission tomography/computed tomography and the results showed that there were multiple bone metastases already present. This was the first English case report of invasive lobular carcinoma of the breast metastasizing to the uterus, stomach, bladder, and bones with multiple signet-ring-cell variations. This study shares our reasons for misdiagnosing and opinions on diagnosing and treating for this kind of cases.

Temporal observation of endoscopic and histological findings of gastritis after administration of an immune checkpoint inhibitor: a case report

A 71-year-old Japanese man was treated with 200 mg of pembrolizumab for lung adenocarcinoma with multiple bone metastases at the Department of Respiratory Medicine of Kameda General Hospital. After 19 treatment courses, he complained of epigastric pain before meals. Upper gastrointestinal endoscopy showed multiple erosions in the gastric antrum, and antacids were administered at follow-up. After 27 treatment courses, the patient underwent another endoscopy because of anorexia. The erosions were enlarged and had increased from the gastric antrum to the greater curvature of the body. Histological biopsy showed lymphocytic infiltration with a predominance of CD8-positive T cells. The patient had previously been treated for Helicobacter pylori infection, and we suspected drug-induced gastritis due to the administration of immune checkpoint inhibitors in the course of the disease. Pembrolizumab was discontinued, and the patient’s symptoms gradually improved. Endoscopic examinations were performed 2, 5, and 9 months after discontinuation of pembrolizumab, and improvement in mucosal findings and decreased lymphocyte infiltration were confirmed each time. The patient has remained without any relapse of symptoms for more than 1 year after discontinuing treatment.

Balloon kyphoplasty for a single vertebra with multiple bone metastases from prostate cancer improved low back pain: A case report

Balloon kyphoplasty for a single vertebra with multiple bone metastases from prostate cancer improved low back pain: A case report

Bilateral Choroidal Metastases In Triple-Negative Breast Cancer: Radiotherapy And Eribulin For Vision Preservation And Prolong Survival

Introduction: Choroidal metastases are infrequent in breast cancer, but if they present, they usually signify the disseminated disease and poor prognosis. The challenges in treating choroidal metastases are not only to prolong survival but also to preserve vision, improving the quality of life. Case Presentation: Our patient was firstly diagnosed with stage-three triple-negative breast cancer at the age of 32 years. She had surgery, adjuvant chemotherapy with anthracycline regime, as well as adjuvant radiotherapy. Her disease firstly recurred two years later with pleural effusion, but it was controlled with six cycles of docetaxel. She was in remission until ten years later when she presented with a worsening dry cough and progressive blurring of vision in both eyes. CT restaging showed multiple sub-centimeter bilateral lung nodules, singular pleural metastases, and multiple bone metastases. Choroidal metastases were also confirmed with the ophthalmological assessment which includes CT of the orbit. She received short-course palliative radiotherapy followed immediately by eribulin. Then, she started monthly bisphosphonates. She was able to read again four months after radiotherapy, and her vision remains normal to date. The latest PET scans showed no FDG avid disease in the lungs with pleural metastases significantly reduced in size. Bone metastases remain stable and asymptomatic. It has been nearly four years since the diagnosis of choroidal metastases. She is still on eribulin at an adjusted dose and interval. She remains asymptomatic from her bone, lung, and choroidal metastases. Conclusions: Short-course radiotherapy to the orbit, followed by continuous administration of eribulin, can lead to prolonged survival with a good quality of life in triple-negative breast cancer with choroidal metastases

MRNA and small RNA gene expression changes in peripheral blood to detect internal Ra-223 exposure

Purpose Excretion analysis is the established method for detection of incorporated alpha-emitting radionuclides, but it is laborious and time consuming. We sought a simplified method in which changes in gene expression might be measured in human peripheral blood to detect incorporated radionuclides. Such an approach could be used to quickly determine internal exposure in instances of a radiological dispersal device or a radiation accident. Materials and methods We evaluated whole blood samples from five patients with castration-resistant prostate cancer and multiple bone metastases (without visceral or nodal involvement), who underwent treatment with the alpha emitting isotope Radium-223 dichloride (Ra-223, Xofigo®). Patients received about 4 MBq per cycle and, depending on survival and treatment tolerance, were followed for six months. We collected 24 blood samples approximately monthly corresponding to treatment cycle. Results Firstly, we conducted whole genome screening of mRNAs (mRNA seq) and small RNAs (small RNA seq) using next generation sequencing in one patient at eight different time points during all six cycles of Ra-223-therapy. We identified 1900 mRNAs and 972 small RNAs (222 miRNAs) that were differentially up- or down-regulated during follow-up after the first treatment with Ra-223. Overall candidate RNA species inclusion criteria were a general (≥|2|-fold) change or with peaking profiles (≥|5|-fold) at specific points in time. Next we chose 72 candidate mRNAs and 101 small RNAs (comprising 29 miRNAs) for methodologic (n = 8 samples, one patient) and independent (n = 16 samples, four patients) validation by qRT-PCR. In total, 15 mRNAs (but no small RNAs) were validated by methodologic and independent testing. However, the deregulation occurred at different time points, showing a large inter-individual variability in response among patients. Conclusions This proof of concept provides support for the applicability of gene expression measurements to detect internalized alpha-emitting radionuclides, but further work is needed with a larger sample size. While our approach has merit for internal deposition monitoring, it was complicated by the severe clinical condition of the patients we studied.

Secondary myelodysplastic syndromes identified via next-generation sequencing in a non-small cell lung cancer patient

BackgroundMyelodysplastic syndrome (MDS) is a group of clonal disorders characterized by ineffective and dysplastic hematopoiesis in the bone marrow with a high risk of progression to leukemia. Many studies have demonstrated that chemo-radiotherapy for cancer patients and exposure to certain chemicals may increase the risk of secondary MDS, which is characterized by specific chromosomal abnormalities and genomic alterations. Since next-generation sequencing (NGS) has been widely used for the diagnosis of cancer patients, advanced analysis of the sequencing data may provide supplementary information for secondary MDS.Case presentationA male patient with non-small cell lung cancer (NSCLC) and bone metastases has presented distal obstructive inflammation, the enlargement of the left hilar, mediastinal lymph node metastases, and multiple bone metastases. This patient has undergone long-term exposures to certain chemicals. Moreover, the deletion of chromosome 7 and 5q is detected in his peripheral blood sequencing, indicating secondary MDS, subsequently confirmed by bone marrow examination.ConclusionIn this case, an NSCLC patient was diagnosed with secondary MDS via NGS analysis, indicating that the NGS analysis may serve as supplementary for diagnosis of secondary MDS and provide useful information of therapeutic regimens for subsequent-line treatment of EGFR-mutated lung cancer. To the best of our knowledge, this is the first report of acquired MDS in a lung adenocarcinoma patient.

A Case of Solitary Metastatic Deposit in the Orbital Rim from Follicular Thyroid Cancer

Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, following papillary carcinoma. Metastasis to the orbital rim from FTC is very rare. We recently experienced a case of FTC with metastasis to the orbital rim in a 74-year-old woman, who initially presented with a huge thyroid mass and an asymptomatic solitary orbital rim lesion. The solitary orbital rim lesion was suspected to be a separate disease entity such as lymphoma from the preoperative imaging, but bone metastasis from FTC was finally confirmed after orbital rim resection and total thyroidectomy. During follow-up, the patient presented multiple bone metastasis, so the solitary orbital rim lesion was considered a clinical sign of systemic metastasis from FTC. Therefore, we present this unique case with a review of the literature.

Unusual hypocalcaemia in breast cancer relapse with multiple bone metastasis

Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis.Learning pointsSevere hypocalcaemia can a presenting symptom for breast cancer relapse.

Breast cancer patients with isolated bone metastases and oligometastatic bone disease show different survival outcomes

In this study, we planned to investigate the clinical course of patients with breast cancer with oligometastatic bone disease (OMBD). The patients were grouped according to the characteristics and the sites of metastases. Group I included 928 patients without metastasis. Group II, the OMBD group, included 68 patients. Group III, the widespread metastasis group, comprised 185 patients with multiple bone metastases and/or solid organ metastases. The mean overall survival of the groups was 16.7 ± 0.3 years in group 1, and 7.8 ± 0.8 and 5.9 ± 0.4 years in groups 2 and 3, respectively (p < 0.001 for the comparison of all three groups together; p < 0.001 for group 1 vs. 2 and 3) and (p = 0.037 for group 2 vs. group 3). In the subgroup survival analysis of patients in group 2 (OMBD), the mean and median survival was 5.5 ± 0.8 and 4.0 ± 0.8 years vs. 9.2 ± 0.98 and 9.0 ± 1.05 years in patients with more than one bone metastasis and single bone metastasis, respectively (p = 0.019). OMBD seems to be a different disease than breast cancer with isolated bone metastases. The high risk of developing OMBD, especially following locoregional recurrence, increases the importance of locoregional therapy in large T and N stage tumors.

Prognostic Factors Influencing Survival and a Treatment Pattern Analysis of Conventional Palliative Radiotherapy for Patients with Bone Metastases.

Background: Treatment indication for bone metastases is influenced by patient prognosis. Single-fraction radiotherapy (SFRT) was proven equally effective as multiple fractionation regimens (MFRT) but continues to be underused. Objective: Primary objectives: (a) to identify prognostic factors for overall survival and (b) to analyze treatment patterns of palliative radiotherapy (proportion of SFRT indication and predictive factors of radiotherapy regimen) for bone metastases. Methods: 582 patients with bone metastases who underwent conventional radiotherapy between January 1st 2014–31 December 2017 were analyzed. The Cox proportional hazard model was used to identify predictors of overall survival. For the treatment pattern analysis, 677 radiotherapy courses were evaluated. The logistic regression model was used to identify potential predictors of radiotherapy regimen. Results: The 3-year overall survival was 15%. Prognostic factors associated with poor overall survival were multiple bone metastases [hazard ratio (HR = 5.4)], poor performance status (HR = 1.5) and brain metastases (HR = 1.37). SFRT prescription increased from 41% in 2017 to 51% in 2017. Predictors of SFRT prescription were a poor performance status [odds ratio (OR = 0.55)], lung (OR = 0.49) and urologic primaries (OR = 0.33) and the half-body lower site of irradiation (OR = 0.59). Spinal metastases were more likely to receive MFRT (OR = 2.09). Conclusions: Based on the prognostic factors we identified, a selection protocol for patients candidates for palliative radiotherapy to bone metastases could be established, in order to further increase SFRT prescription in our institution.

Clinical Features and Serological Markers Risk Model Predicts Overall Survival in Patients Undergoing Breast Cancer and Bone Metastasis Surgeries.

BackgroundSurgical therapy of breast cancer and bone metastasis can effectively improve the prognosis of breast cancer. However, after the first operation, the relationship between preoperative indicators and outcomes in patients who underwent metastatic bone surgery remained to be studied. Purpose 1. Recognize clinical and laboratory prognosis factors available to clinical doctors before the operation for bone metastatic breast cancer patients. 2. Develop a risk prediction model for 3-year postoperative survival in patients with breast cancer bone metastasis.MethodsFrom 2014 to 2020, patients who suffered from breast cancer bone metastasis and received therapeutic procedures in our institution were included for analyses (n=145). For patients who underwent both breast cancer radical surgery and bone metastasis surgery, comprehensive datasets of the parameters of interest (clinical features, laboratory factors, and patient prognoses) were collected (n=69). We performed Multivariate Cox regression to identify factors that were associated with postoperative outcome. 3-year survival prediction model and nomograms were established by 100 bootstrapping. Its benefit was evaluated by calibration plot, C-index, and decision curve analysis. The Surveillance, Epidemiology, and End Results database was also used for external validation.ResultsRadiotherapy for primary cancer, pathological type of metastatic breast cancer, lymph node metastasis, elevated serum alkaline phosphatase, lactate dehydrogenase were associated with postoperative prognosis. Pathological types of metastatic breast cancer, multiple bone metastasis, organ metastases, and elevated serum lactate dehydrogenase were associated with 3-year survival. Then those significant variables and serum alkaline phosphatase counts were integrated to construct nomograms for 3-year survival. The C-statistic of the established predictive model was 0.83. The calibration plot presents a graphical representation of calibration. In the decision curve analysis, the benefits are higher than those of the extreme curve. The receiver operating characteristic of the external validation of the model was 0.82, indicating a favored fitting degree of the two models.ConclusionOur study suggests that several clinical features and serological markers can predict the overall survival among the patients who are about to receive bone metastasis surgery after breast cancer surgery. The model can guide the preoperative evaluation and clinical decision-making for patients. Level of evidence Level III, prognostic study.

Efficacy of 3 Monthly versus Monthly Zoledronic Acid on Bone Metastasis

Background: Bone metastatic disease affect a patient’s quality of life. Aim: Evaluating possible stratification factors affecting the efficacy of different schedules of zoledronic acid on SREs. Patients and Methods: A randomized, clinical trial at Zagazig university hospitals. 108 Patients were enrolled to receive zoledronic acid 4 mg (A and B groups=12 and 4 weeks, respectively) for 2 years. Results: Regarding age, tumour type, types of bone metastasis and number of bone metastasis, there was an insignificant difference between both groups. However, 3 monthly regimen of zoledronic acid gave better results in solitary than multiple bone metastases. Regarding pretreatment ECOG, there was an insignificant difference between between both groups. However, 3 monthly regimen of zoledronic acid gave better results in pre-treatment ECOG 1and ECOG 2 than ECOG 3. Conclusion: A 3-monthly regimen of zoledronic acid is more effective in management of solitary or few sites of bone metastasis, osteoblastic bony lesions and patients with good performance status. Recommendations: We recommend a larger sample size and the study should include a homogenous groups of patients so we can judge well on different stratifications factors that can affect efficacy of 3- monthly regimen of zoledronic acid.

The Role of Proteasome Inhibitors in Multiple Myeloma Bone Disease and Bone Metastasis: Effects on Osteoblasts and Osteocytes

The alterations of bone remodeling are typical of multiple myeloma (MM) patients where the uncoupled and unbalanced bone remodeling caused the onset of osteolytic lesions. Moreover, bone metastasis occurs in the majority of patients with breast and prostate cancer. Skeletal-related events negatively impact on quality of life by increasing the vulnerability to fractures. Several bone-targeting treatments have been developed to control bone pain and pathological fractures, including bisphosphonates and Denosumab. Nevertheless, these agents act by inhibiting osteoclast activity but do not improve bone formation. Proteasome inhibitors (PIs) have shown bone anabolic effects and encouraging results in stimulating osteoblast differentiation and bone healing. Among these, the first-in-class bortezomib and the second-generation PIs, carfilzomib, and ixazomib regulate the bone remodeling process by controlling the degradation of several bone proteins. PIs have been recently proven to also be efficacious in blocking MM-induced osteocyte death providing new possible therapeutic use in the management of bone loss. PIs have significant side effects that limit their use as bone anabolic strategy. Multiple alternative approaches have been made. The conjugation of PIs with bisphosphonates, which can target them to bone, showed good results in terms of bone anabolic activity. However, the clinical implications of these effects require further investigations.

Pathochistological and immunohistochemical study in small intestine metastasis as first clinical expression of invasive lobular breast carcinoma: Prognosis and complex treatment

The gastrointestinal metastases (GIM) of breast carcinoma (BC) are a rare clinical finding, even more rarely diagnosed as initial symptoms at unknown BC. We present a 50-year-old woman with metastases in the terminal ileum combined with multiple bone metastases from an unknown invasive carcinoma of left mammary gland. Gastrointestinal metastases are rarely observed in invasive lobular breast carcinoma. Differential diagnosis between intestinal metastases from primary BC and primary intestinal neoplasm is extremely difficult. Determination of tumor pathohistogenesis require careful pathohistological and immunohistochemical analysis. Complex treatment follows the primary neoplasm principles. The prognosis in such clinical cases is unfavorable, but after timely complex oncological treatment, including emergency operation, chemotherapy, hormone and target therapy, 36 monthly survival is achieved. Keywords: gastrointestinal metastases; invasive lobular breast carcinoma; pathohistological analysis; immunohistochemical analysis; complex treatment.

Calcitonin Changed During Pregnancy in MEN2A With MTC Patient: A Case Report

Background: The diagnosis of MTC during pregnancy was challenging. No definite calcitonin (Ct) cut-off level during pregnancy was defined. Moreover, cytology analysis accuracy in MTC was lower than other thyroid cancers. Stevenson et al. reported that the plasma Ct levels in pregnant women were much higher than normal women. The change in Ct levels during pregnancy was not well described. In this report, we present a case of a pregnant woman with recurrent MTC. The change in Ct levels during pregnancy, diagnosis methods, and proper management were presented here. Clinical Case: A 31-year Thai woman, gravida 2, para 0 at 17 weeks of pregnancy, previously diagnosed with MTC and treated with total thyroidectomy and neck dissection seven years ago. During antenatal care at 14 weeks of pregnancy, the Ct level was 126 pg/ml (raised from 34 pg/ml seven years ago). The neck’s USG demonstrates vascularized hypoechoic lesion at the right thyroid bed with multiple nodules. The Ct wash-out test from this lesion was 200,000 pg/ml. The cytology study showed several clusters of atypical cells possessing monotonous round eccentric nuclei, and the IHC for Ct was positive. Genetic analysis revealed germline mutation in exon 10 of the RET proto-oncogene (NM_020975.4: c.1858T>G, p.C620G). Finally, MEN 2A with recurrent MTC was diagnoses during pregnancy. The other associate diseases were not found (normal urine metanephrines and plasma calcium levels). The Ct level raised highest to 324 pg/ml at 28 weeks of pregnancy and declined to 236 pg/mL a few days after delivery. Within six weeks, the Ct levels raised again (335 and 362 pg/ml at six weeks and three months after delivery).After giving birth, she underwent neck dissection; The Ct level at one month after surgery was still elevated (85 pg/ml). The CT of the chest, abdomen, and bone scan revealed multiple LN and bone metastasis. She regularly followed up in the oncology clinic and did well until nowadays (two years after delivery). After birth, her son could not pass meconium. Causing underwent exploratory laparotomy with double end ileostomy at day nine of life. The histopathology study from serial bowel biopsy demonstrated aganglionosis of the entire colon, which compatible with Hirschsprung’s disease. Genetic study from colonic tissue and blood confirmed the diagnoses of MEN 2A like his mother. Total thyroidectomy before five years of age and investigate for other associated diseases were planned. Conclusion: The Ct levels were elevated throughout the pregnancy. Transient declined of Ct levels during delivery and raised within six weeks suggest that pregnancy did not affect the Ct levels. In this report, we want to present the change of Ct levels during pregnancy, emphasize the diagnosis of MTC and MEN2A in pregnant women, which may change the patient’s prognosis. Not only in the patients but also in their families. Clinicians should be aware of the management of these patients.

Analyses of the clinical characteristics of 49 cases of malignancy with multiple bone lesions as the first manifestation

Abstract Objective To investigate the clinical features of several cases of malignancy with multiple bone lesions as the first manifestation. Methods Forty-nine cases of malignancy with multiple bone lesions as the first manifestation were retrospectively analyzed from May 2018 to July 2019. All patients complained of “pain at the site of bone lesion” upon admission. Baseline patient information, such as age, gender, location of bone lesions, etiology, diagnosis method, time of onset was collected. Results The median age of the patients was 56 years old, of which 83.7% (41/49) were aged ≥50 years. The median time of onset was 2 months. Among the cases, 40 were confirmed as solid tumor bone metastasis, whereas the remaining 9 cases as hematological system tumor. Lung cancer and multiple myeloma were the main tumor types, accounting for 40.8% (20/49) and 16.3% (8/49), respectively. Other common causes were seven cases of cancer affecting the digestive system (three cases of liver cancer, three cases of gastric cancer, and one case of esophageal cancer), as well as seven cases of unknown primary cancer. Half of the solid tumors had only multiple bone metastases but no other distant metastasis. Conclusion Multiple bone lesions accompanied by pain may be the first clinical manifestation in various malignant tumors. The common tumor types were lung cancer, multiple myeloma, and digestive system tumor. It is more common in people aged 50 years and older. Multiple bone lesions might be the only metastasis site of some solid tumors, and its mechanism needs further investigation.