Multiple Lung Metastases Research Articles

Abstract A063: The role of JAK/STAT3 signaling in lung premetastatic niche formation and progression

Abstract Pancreatic ductal adenocarcinoma (PDA) is a highly deadly disease with a five-year survival rate of only 13%. Oncogenic KRAS (Kras) is a near-universal driver of PDA, and its activity is required for the formation of PDA precursor lesions, pancreatic intraepithelial neoplasia (PanIN). PanIN formation is accompanied by fibrosis and immune cell infiltration, creating a precursor tumor microenvironment that is maintained and evolves through disease progression. Our previous work has demonstrated that Kras in epithelial cells drives fibroblast activation during very early stages of pancreatic tumorigenesis and that fibroblast reprogramming occurs in a JAK/STAT3 signaling-dependent manner. Other groups have described that pancreatic cancer cells secrete specific factors to prime the liver and lung through immunomodulation and extracellular matrix remodeling, forming the premetastatic niche (PMN). Additionally, recent papers in the field have suggested a role for JAK/STAT3-reprogramming in the formation of the PMN during pancreatic tumorigenesis. Presently, it remains to be elucidated at what stage of PDA tumorigenesis the PMN is initiated, as well as the mechanisms underlying formation. In a pilot experiment, we induced pancreas specific Kras until mice had PanIN lesions but no overt malignancy. We then harvest the pancreas and lung for single cell RNA sequencing. Here, results showed that when Kras is expressed within the pancreas of a mouse, fibroblasts are reprogrammed within the lung, prior to pancreatic tumor formation. Additionally, data indicates JAK/STAT3 signaling activation present within these fibroblasts. We also used multiple lung metastasis models, both spontaneous and tail vein injection, to show persistence of this reprogramming. This suggests that pancreatic Kras expression can systemically reprogram fibroblasts to form a PMN more capable of seeding cancer cells. Our in vitro studies have showed similar results as lung fibroblasts treated with Kras ON conditioned media show increased pSTAT3. Furthermore, using multiplex ELISA on iKras conditioned media, we have identified multiple promising secreted factor hits that may play a role in lung fibroblast reprogramming. Ongoing studies aim to define the mechanism of pulmonary fibroblast reprogramming in the context of the PMN and to assess the role of pSTAT3+ fibroblast reprogramming on establishment of pulmonary metastases. Citation Format: Emily Lasse Opsahl, Carlos E Espinoza, Katelyn L Donahue, Ahmed M Elhossiny, Padma Kadiyala, Allison C Bischoff, Mary Poggi, Yaqing Zhang, Jiaqi Shi, Timothy Frankel, Marina Pasca di Magliano. The role of JAK/STAT3 signaling in lung premetastatic niche formation and progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A063.

Elevations of neutrophil-to-lymphocyte ratio and C-reactive protein over time as a precursor to anaplastic transformation of papillary thyroid carcinoma: a case report

BackgroundPapillary thyroid carcinoma rarely undergoes anaplastic transformation. Some risk factors for anaplastic transformation of thyroid cancer are known, but such transformation is difficult to predict in practice. We report a case demonstrating elevations of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) over time as a precursor to anaplastic transformation of thyroid carcinoma.Case presentationThe patient was an 89 year-old woman with a history of chronic aortic dissection. She was referred to our department after her local doctor detected thyroid nodules. She had previously been found to have multinodular goiter and enlarged left cervical lymph nodes on computed tomography. Her chief complaint was cervical discomfort and hoarseness. Blood tests revealed: white blood cells (WBCs), 4900 /µL; CRP, 0.29 mg/dL; neutrophils, 64.4%; and lymphocytes, 25.4%. A 21 mm mass was identified in the upper left lobe. Left III (16 mm) and left VI (16 mm) lymph node were enlarged on ultrasonography. Fine-needle aspiration cytology diagnosed malignant papillary carcinoma. However, due to the advanced age and medical history of the patient, a non-surgical policy was implemented. The primary tumor grew to 4 cm in diameter by 9 months after diagnosis, and blood tests showed: WBC, 7700 /µL; CRP, 0.18 mg/dL; neutrophils, 65.3%; and lymphocytes, 22.3%. By 10 months after diagnosis, the tumor had increased rapidly in diameter to 8 cm, with blood tests showing: WBC, 6500 /µL; CRP, 1.01 mg/dL; neutrophils, 68.2%; and lymphocytes, 19.3%. Anaplastic transformation of papillary thyroid carcinoma was diagnosed, and the patient was placed on treatment under a policy of best supportive care. Multiple lung metastases appeared 11 months after diagnosis, and blood test results showed: WBC, 13,300 /μL; CRP, 11.28 mg/dL; neutrophils, 93.6%; and lymphocytes, 2.3%. Unfortunately, the patient died of disease progression 63 days after identification of undifferentiated metastasis.ConclusionsChances to see the natural history of anaplastic transformation of thyroid cancer are rare. Elevations in NLR and CRP over time may be precursors to anaplastic transformation.

Total management of hemangiopericytoma/solitary fibrous tumor of the buttock: A case report.

Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review. A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up. Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome. Long-term monitoring for potential complications remains necessary.

Brain metastases in testicular cancer: A single-institution experience in Guatemala.

e17019 Background: Brain metastases secondary to germ cell tumors develop in 2 to 3% of patients, in addition to implying a poor prognosis, its incidence in advanced stages increases to 10-15%. The European Urology Association guidelines recommend performing imaging studies using MRI or brain contrasted tomography to rule out metastases in patients with multiple lung metastases, or high beta subunit of human Chorionic Gonadotropin (β-HCG) values, or those in the poor-prognosis International Germ Cell Cancer Collaborative Group (IGCCCG) risk group. Methods: Retrospective descriptive study in patients with brain metastasis for testicular cancer at the Liga Nacional Contra el Cáncer – INCAN Guatemala, from 2018 to 2022. From medical records, we obtained: demographic, clinico-pathological and treatment data. Median was calculated for age, while frequencies and percentages were computed for the categorical variables. Results: Of the 238 patients diagnosed with testicular cancer, 22% (52) presented a β-HCG above 5,000 IU/L, of which 27% (14) developed brain metastases with a mean age of 28 years. Corresponding to 6% of the total cases studied. Among histological subtypes the most common was choriocarcinoma (43%), follow by mixed germ cell cancer (36%), embrionary carcinoma (14%) and classic seminoma (7%). All of the patients belonged to prognostic group S2. Most patients reported first symptom was headache (42%), followed by seizures (21%), cognitive dysfunction (15%), motor dysfunction (10%) and others (12%). Management of these patients included: orchidectomy in all of them, 57% (8) of patients died, of them 50% (4) of patients died before any other therapy. The rest of them, received chemotherapy and none received radiotherapy or surgery for the brain metastases. Conclusions: The presence of brain metastases in testicular cancer increases the mortality produced by the disease as previously reported in other regions of the world, reason why the early suspicion of it, should prompt the evaluation with a brain MRI or computed tomography.

Renal Pelvic Cancer with Multiple Lung Metastases in a Patient with Polycystic Kidney Disease, Initially Diagnosed as Non-small Cell Lung Cancer: An Autopsy Case Report.

A 64-year-old man with autosomal dominant polycystic kidney disease (ADPKD) on hemodialysis presented with multiple lung masses. A computed tomography (CT)-guided biopsy revealed non-small-cell lung cancer (NSCLC). A cavitary mass in the right lung indicated primary NSCLC (cT2N1M1a, stage IVA). Pembrolizumab was initiated because of a high programmed death-ligand 1 (PD-L1) expression (90%). On day 10 post-treatment, he developed acute respiratory failure with diffuse ground-glass opacities on chest CT, indicative of pembrolizumab-induced lung injury. Despite steroid pulse therapy, the patient died on day 13. An autopsy revealed left renal pelvic cancer with lung metastases, highlighting the diagnostic challenges in ADPKD.

Case Report: Acute arterial occlusion of the right lower extremity due to left atrial invasion from pulmonary metastases of thyroid cancer

Cardiac metastases of thyroid cancer are rare. The most common metastatic route is through lymphatic or hematogenous spread to the right side of the heart. Direct invasion of metastases from other adjacent organs to the left side of the heart is even rarer. In many cases, the disease progresses asymptomatically, and symptoms appear only when it is already fatal. A 68-year-old woman underwent total thyroidectomy and right-side lymph node dissection for papillary thyroid cancer and multiple lung metastases 7 years previously. The patient was referred to our hospital due to sudden pain in the right lower extremity and motor disturbance. Computed tomography revealed acute arterial occlusion of the right lower extremity due to tumor dispersal from a left atrial invasion caused by multiple pulmonary metastases of thyroid cancer, and only emergency thrombectomy was performed. Although blood flow was restored, the patient died of respiratory failure 2 months after the procedure. Radical resection is considered difficult in cases of direct invasion of metastases from other adjacent organs because multiple metastases have often already occurred. Therefore, in the terminal stage, it might be too invasive to resect a tumor only to prevent embolism recurrence. The treatment strategy should depend on the patient's prognosis and choice.

Long-term survival after surgical resection for bone metastasis from pancreatic cancer: A case report.

Pancreatic cancer (PC) is highly malignant and metastatic; however, bone metastases are rare. Although the effectiveness of conversion surgery for distant metastases of PC has been reported in a few cases, there are no reports on surgical resection for bone metastases. Here, we report a case of long-term survival after resection of bone metastasis from PC. A 60-year-old woman underwent pancreaticoduodenectomy after neoadjuvant chemoradiotherapy for pancreatic head cancer. At 28 months after surgery, multiple lung metastases from PC were diagnosed, and chemotherapy was administered. After 59 months, chemotherapy was terminated because all target lesions had disappeared on imaging. At 77 months after the initial surgery, bone metastasis in the left 9th rib was detected by positron emission tomography/computed tomography, which was performed due to elevated carbohydrate antigen 19-9 levels. Chemotherapy was readministered as the initial treatment. Subsequently, due to the long-term well-controlled status of the recurrence site and the absence of other metastases, thoracoscopic-assisted partial resection of the left 9th rib was performed 128 months following pancreaticoduodenectomy. Pathological examination revealed adenocarcinoma metastasis from PC. The patient is currently alive without recurrence 44 months after resection for bone metastasis and 172 months after the initial surgery. Surgical resection may be favorable in patients with bone metastasis of PC that is well-controlled with chemotherapy.

Radiomic-Based Prediction of Lesion-Specific Systemic Treatment Response in Metastatic Disease.

Cancer is a heterogenous, dynamic target. Individual patients, lesions, and cell populations may present with different characteristics and varying sensitivities to anticancer therapies. The purpose of this study was to investigate the utility of image-derived (radiomic) biomarkers for prediction of lesion-specific treatment response. Using a database of serial imaging from a Phase III clinical trial (NCT01440088), all visible lung metastases were contoured on chest computed tomography performed at baseline and after 2 cycles of chemotherapy. Metastatic leiomyosarcoma patients received either doxorubicin monotherapy (DM) or doxorubicin plus evofosfamide (DE). Percent change in volume with respect to baseline was evaluated as a metric of treatment response. Lesions that experienced a positive volume change greater than 50% were labeled as 'progressors'; all other lesions were labeled as 'non-progressors'. Radiomic features were extracted at baseline from the whole lesion and three peritumoral regions using PyRadiomics (version 3.0.1). Features were compared using the Mann-Whitney U-test and further used to classify between response categories. Logistic classification models were evaluated with 10-fold cross-validation using Area Under the Curve for the Receiver Operating Characteristic (AUROC) and Precision-Recall (AUPRC) curves as measures of model performance. Significance was evaluated by permutation tests. All code used to derive features is open source and available for download. In total, 204 lung metastases from 80 patients were evaluated. The fraction of progressing lesions was 19% and 27% for the DM and DE regimes, respectively. Differences in individual lesion response were observed in 20% of patients with multiple lung metastases. Significant differences in entropy were observed between response categories (false discovery rate < 5% after multiple testing correction): interior regions for lesions receiving DM, and peripheral regions for lesions receiving DE. The best performing models for the DM and DE regimens had AUROC of 0.87 and 0.76 and AUPRC 0.60 and 0.50, respectively (p < 0.05). Predicting lesion-specific responses using radiomic features represents a paradigm shift. Lesion-specific radiomic models indicate a 2 to 3-fold increase in predictive capacity in comparison to a no-skill classifier. These models, although preliminary, achieved a strong predictive value and could be used to predict lesion-specific treatment response.

Successful Retreatment of Metastatic Triple-negative Breast Cancer With Immune Checkpoint Inhibitors and Chemotherapy.

The efficacy of retreatment with immune checkpoint inhibitors (ICIs) in programmed death-ligand 1 (PD-L1) positive metastatic or recurrent triple-negative breast cancer (mTNBC) remains unknown. We report a case of a patient with recurrent triple-negative breast cancer who was successfully treated with two different ICIs in combination with chemotherapy. A 60-year-old female patient was treated with neoadjuvant chemotherapy consisting of epirubicin + cyclophosphamide (EC) followed by docetaxel (DTX). The tumor shrank with EC, but progressed with DTX. One year after the surgery, the patient presented with multiple lung metastases. The patient received combination therapy with atezolizumab and nab-paclitaxel and achieved a partial response (PR). However, the disease progressed after 6 months. She received eribulin as second-line chemotherapy for 4.5 months, and her treatment was changed to pembrolizumab, carboplatin, and gemcitabine as third-line chemotherapy. The tumor immediately reduced and disappeared after three cycles of this treatment and achieved PR. This case illustrated that retreatment with ICIs was effective.

Cerebral tumor embolism from thyroid cancer treated by mechanical thrombectomy: illustrative case.

Development in mechanical thrombectomy is progressing dramatically. Tumor embolism has been rarely reported on the basis of pathological study of the retrieved thrombus. Herein, the authors report a case of cerebral tumor embolism from advanced thyroid cancer, which was successfully treated with mechanical thrombectomy. A 57-year-old man was diagnosed with thyroid cancer with multiple lung metastases and chemotherapy was planned. He experienced left hemiparesis and was bought to the emergency section of the authors' hospital. Magnetic resonance angiography revealed right internal carotid artery occlusion and endovascular treatment was performed. Using a combination of aspiration catheter and stent retriever, white jelly-like embolus was retrieved. The pathological study demonstrated thyroid cancer embolism. Pulmonary vein invasion following lung metastasis of thyroid cancer was most presumably the cause of the tumor embolism. Lung metastasis invading the pulmonary vein may be a cause of tumor embolism. Mechanical thrombectomy using a combination of stent retriever and aspiration catheter is effective in removing the tumor embolus and the pathological examination of the embolus is essential.

The Outcome of Discontinuing Tyrosine Kinase Inhibitors in Advanced Sarcoma Following a Favorable Tumor Response to Antiangiogenics Therapy.

(1) Background: The use of antiangiogenic TKIs (AA-TKIs) has recently emerged as a major paradigm shift in the treatment of advanced sarcoma. However, the feasibility of drug holidays for patients demonstrating a very favorable response remains unknown. (2) Methods: We aim to explore the outcomes of patients with advanced sarcoma who discontinued AA-TKIs after a (near-) complete remission or were long-term responders. Patients with advanced disease were included if they had bilateral or multiple lung metastases, extrapulmonary recurrence, a short disease-free interval, etc., at the initiation of AA-TKIs. (3) Results: A total of 22 patients with AA-TKI discontinuation were analyzed, with a median follow-up of 22.3 months post-discontinuation. Prior to discontinuation, there were four drug-induced complete remissions (CRs), twelve surgical CRs, and six long-term responders. Disease progression was observed in 17/22 (77.3%) patients, with a median of 4.2 months. However, since the majority were still sensitive to the original AA-TKIs and amenable to a second surgical remission, 7 out of these 17 patients achieved a second CR after disease progression and were thus considered as relapse-free post-discontinuation (pd-RFS). Therefore, the pd-RFS and post-discontinuation overall survival (pd-OS) in the last follow-up were 12/22 (54.5%) and 16/22 (72.7%), respectively. Remarkably, surgical CR and drug tapering off (versus abrupt stopping) were associated with a greater pd-RFS and pd-OS (p < 0.05). Furthermore, higher necrosis rates (p = 0.040) and lower neutrophil-to-lymphocyte ratios (NLR) (p = 0.060) before discontinuation tend to have a better pd-RFS. (4) Conclusions: Our results suggest that AA-TKI discontinuation with a taper-off strategy might be safe and feasible in highly selected patients with advanced sarcoma. Surgical CR, NLR, and tumor necrosis rates before discontinuation were potential biomarkers for AA-TKI withdrawal.

Gastric carcinosarcoma with FGFR2 amplification under long-term control with pazopanib: a case report and literature review

BackgroundGastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib.Case presentationA 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor–node–metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months.ConclusionsWe report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

A CASE OF RENAL CELL CARCINOMA WITH SMALL INTESTINE METASTASIS DURING NIVOLUMAB PLUS IPILIMUMAB

A 71-year-old man with a history of hoarseness and right upper extremity numbness was referred to our department for evaluation of an intrathoracic mass that was detected on chest radiography and a right kidney tumor observed on computed tomography (CT). Histopathological examination of percutaneous kidney biopsy and bronchoscopic lung biopsy specimens revealed renal clear cell carcinoma with multiple lung metastases. The patient showed a poor risk based on the International Metastatic renal cell carcinoma Database Consortium score, and nivolumab plus ipilimumab were initiated as first-line therapy. His symptoms gradually improved, following four courses of nivolumab plus ipilimumab treatment, and CT revealed shrinkage of all lesions. However, he developed diarrhea, rash, anemia, and elevated serum C-reactive protein levels (CRP) following this therapy. Diarrhea and rash were considered immune-related adverse events, and he was treated with oral prednisolone and topical corticosteroid. Nivolumab administration was discontinued because anemia worsened together with elevated serum CRP levels despite improvement in diarrhea. He subsequently developed constipation and abdominal bloating, following further treatment for 4 months. CT revealed intestinal tumor-induced intussusception, necessitating partial resection of the small intestinal tumor, which was histopathologically diagnosed as metastases. Both anemia and elevated CRP improved postoperatively. Currently, all metastatic lesions other than the resected intestine have continued to respond to treatment over 12 months after initiation of nivolumab plus ipilimumab therapy.

Left Renal Failure with Lung Metastasis: A Case Report

Background : Lung metastasis is a lung cancer complication that can harm a person’s lung and lessen their ability to breathe fully on exhalation and inspiration. Adrenal glands, the liver, and the pancreas will all be impacted by metastasis, and in a very small percentage of instances, the kidney will also be affected and its function hampered. Here, we describe a case of primary renal cell carcinoma with left kidney failure due to lung metastasis. Metastasis is the process by which cancer cells move to different body organs from the site where they initially developed through the lymphatic and circulatory systems. The fourth stage of cancer, known as metastasis, is typically when the fatality rate increases the most since it affects the body’s organs’ ability to digest food, make bone and tissue repairs, produce blood, and operate normally. Case presentation : Breathlessness, back pain, severe compensated metabolic acidosis, multiple lung metastases in the lateral lung parenchyma, and multiple metastases in the bilateral lung parenchyma were the main complaints of a 70-year-old man with known lung metastases. These appear to be a cannonball. The atrial blood gases (ABG) showed compensated metabolic acidosis, which led to the patient being intubated as a result of the body’s increased oxygen demand. The patient previously experienced a cerebral vascular stroke (which resulted in left-side paralysis), for which he received treatment eight years ago and was subsequently cured. Know the patient is on treatment injection clindamycin, injection linezolid, injection DEXA, injection pantop, injection emset, injection optineuron, tab urimax, syp. duphalac. Conclusion : it is important to take into consideration lung metastasis with primary renal cell carcinoma to left kidney failure differentiation diagnosis, especially in patients with concomitant conditions as they may lead to life-saving intervention for the patient but typically with the patient fourth stage of metastasis have less chance of survival rate. The fiveyear life expectancy for lung metastasis associated primary renal cell carcinoma is approximately seven percent (7%)

Survival of stage 4 primary breast cancer cases after surgery by intrinsic subtype: HER2-positive subtype potentially curable.

e13026 Background: With the incorporation of anti-HER2 agents in the treatment of HER2 positive primary breast cancer, stage 4 disease of this subtype has become potentially curable. However, the duration of clinical CR that is needed be certain that the patient is cured, and therefore the necessary duration of anti-HER2 treatment is uncertain. We address this issue in this presentation. Methods: We present cases of stage 4 primary breast cancer who underwent breast surgery after their distant metastases were controlled, with continued post-operative systemic therapy. There were 52 cases of which the intrinsic subtype as of immunohistochemical analysis was as follows; Luminal A - 7 cases, Luminal B, - 14 cases, Luminal-HER2 - 9 cases, HER2-enriched - 7 cases, and Triple negative -15 cases. The patients were followed up for duration of treatment and overall survival. Results: The average post-operative observation period for all 52 cases was 32.6 months. The five year overall survival rate for HER2-enriched cases was 100%, for Luminal-HER2 cases 80%, for Luminal A cases 80%, for Luminal B cases 55%, and for Triple-negative cases 0%. Of the 16 HER2 positive cases (Luminal-HER2 and HER2 enriched), there was only one death at 48.4 months post-operation. The survival of 5 of 15 surviving HER2 positive cases exceed 60 months (5 years). Of the five, only one at 72.0 months has clinically observable disease (cSD). The remaining 4 cases all are clinically disease free (cCR). Of the 4 cCR cases, only 1 case which originally had multiple lung metastases is continuing anti-HER2 therapy at 90.3 months post-operation. The remaining three discontinued anti-HER2 therapy at 18.1 months (lung metastases CR, observation period 71.7 months), 72.3 months (liver and lymph node metastases CR, observation period 90.3 months), and 101.9 months (liver and bone metastases CR, observation period 102.3 months), respectively. The last case terminated anti-HER2 therapy after testing negative for ERBB2 related genes on liquid biopsy. Conclusions: With the proper incorporation of anti-HER2 therapy, Stage 4 HER2 positive primary breast cancer disease seems to be a potentially curable disease, and anti-HER2 therapy probably can be discontinued in cCR patients after 5 years. Liquid biopsy for tumor related genes (e.g. ctDNA, miRNA) might facilitate decision making.

Outcome of near-infrared fluorescence-navigated pulmonary metastasectomy for hepatocellular carcinoma.

Pulmonary metastasectomy for hepatocellular carcinoma (HCC) is suitable in highly selected patients. However, complete resection is challenging in HCC patients with multiple lung metastases. We aimed to describe the clinical utility and survival outcome of indocyanine green (ICG) fluorescence-navigated resection of HCC lung metastases. From October 2015 to March 2021, 15 HCC patients with pulmonary metastasis underwent near-infra-red (NIR) fluorescence imaging thoracoscopic surgery. ICG was administered through peripheral veins preoperatively. All suspected lesions detected by palpation, white-light thoracoscopy or NIR imaging were resected. After metastasectomy, all patients were followed up at regular intervals of 6-12 months. A total of 90 metastatic HCC nodules were resected in 15 patients. All patients received sublobar resections, during which 89 lesions were removed by wedge resection and 1 lesion was managed via segmentectomy. Under NIR fluorescence imaging, 81 nodules successfully demonstrated fluorescence during the surgery, while 9 metastatic nodules were undetected. The median signal-to-background ratio of the nodules was 3.34. Five patients died and 7 patients relapsed by the end of observation. The median overall survival and disease-free survival were 47.1 and 17.3 months, respectively. The 1-year overall survival and disease-free survival rates were 71.1% and 57.8%, respectively. ICG fluorescence imaging technology is useful for visualization of the peripheral tumours to assist in pulmonary metastasectomy for HCC. In addition, this technology has the potential to detect the small tumour that is missed in preoperative examinations, which might be beneficial for HCC patients with multiple lung metastases.

IgG4-related lung disease with recurrent pulmonary lesions during steroid therapy and difficulty in differentiating from malignancy: a case report

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is characterized by the formation of inflammatory lesions with fibrosis and infiltration of IgG4-positive plasma cells and lymphocytes in various organs of the body. Since the first report of IgG4-related autoimmune pancreatitis, IgG4-RD affecting various organs has been reported; however, only a few reports of IgG4-related lung disease (IgG4-RLD) exist. In this report, we describe a case of IgG4-RLD that was difficult to differentiate from malignancy, and the usefulness of the surgical approach in determining the appropriate diagnosis and treatment plan.Case presentationA 61-year-old man was referred to our hospital after a chest radiograph revealed an abnormal chest shadow. At the time of his first visit, he had a slight fever and dyspnea on exertion. Chest computed tomography (CT) revealed a middle lobe hilar mass with irregular margins and swelling of the right hilar and mediastinal lymph nodes. These findings were not present on CT 1.5 years ago. 18F-fluorodeoxyglucose-positron emission tomography revealed a mass lesion with a maximum diameter of 5.5 cm, maximum standardized uptake value (SUVmax) of 11.0, and areas with high SUV in the hilar and mediastinal lymph nodes. We suspected lung cancer or malignant lymphoma and performed a thoracoscopic lung biopsy to confirm the diagnosis. Histopathological examination revealed no malignant findings, and IgG4-RLD was diagnosed. One month after treatment with prednisolone (PSL), the tumor had shrunk, but a CT scan during the third month of PSL treatment revealed multiple nodular shadows in both lungs. Considering the possibility of malignant complications and multiple lung metastases, we performed thoracoscopic partial lung resection of the new left lung nodules to determine the treatment strategy. Histopathological examination revealed no malignant findings in any of the lesions, and the patient was diagnosed with IgG4-RLD refractory to PSL monotherapy.ConclusionsIgG4-RLD refractory to PSL monotherapy showed changes from a solitary large mass (pseudotumor) to multiple nodules on chest CT. It was difficult to distinguish malignancy from IgG4-RLD based on imaging tests and blood samples alone, and the surgical approach was useful in determining the appropriate diagnosis and treatment plan.

術後多発肺転移を来したA型胸腺腫の2例

術後多発肺転移を来したA型胸腺腫の2例

Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK\xa0double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively

IntroductionAnaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing.Case presentationCase 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib.ConclusionsOur study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

Management of severe hypertension due to lenvatinib in patients with advanced thymic carcinoma

Rationale:Thymic carcinoma (TC) is a malignant mediastinal tumor, and there are no established treatments for pre-treated patients with advanced TC. Recently, lenvatinib was approved for such patients in Japan, ahead of other countries. Higher dose lenvatinib may be more efficacious than conventional treatments, although many patients experience grade 3 hypertension. Therefore, lenvatinib dose reduction remains controversial in terms of efficacy and tolerability.Patient concerns:Case 1 involves a 72-year-old woman who underwent complete resection of TC and was taking cilnidipine and azilsartan for hypertension. Six years later, multiple lung metastases were observed, and lenvatinib was started. Case 2 involves a 60-year-old man with TC, and was taking amlodipine for hypertension. A chest computed tomography showed progression in primary and metastatic lesions, and the patient started lenvatinib.Diagnoses:In both patients, grade 3 hypertension was observed after the administration of lenvatinib.Interventions:In Case 1, lenvatinib dose was reduced 3 times because lenvatinib was not interrupted despite grade 3 hypertension. In contrast, in Case 2, lenvatinib was interrupted when grade 3 hypertension occurred and was resumed after a decrease in blood pressure to baseline.Outcomes:In Case 2, higher tumor regression may have been achieved because of the maintenance of a high dose of lenvatinib compared with that in Case 1.Lessons:Lenvatinib is a promising agent for advanced TC; however, hypertension should be addressed cautiously, especially at the outset of administration. Lenvatinib may have to be appropriately interrupted and resumed as soon as the blood pressure is controlled to maximize efficacy and minimize toxicity.