Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumor resection.

INTRODUCTION: Recycled bone autografts prepared using extracorporeal irradiation (ECIR) or liquid nitrogen freezing (LNF) methods have been used for the reconstruction of skeletal elements after wide resection of sarcomas involving bone tissues. Few reports include long-term follow-up data for histological analyses of recycled autografts, particularly in the case of ECIR autografts. MATERIALS: A total of 34 malignant bone and soft tissue tumors were resected and reconstructed using 11 ECIR- and 23 LNF-recycled autografts; the mean postoperative follow-ups were 14 and 8 years, respectively. ECIR was used for either osteosarcomas or Ewing sarcomas, whereas in addition to these tumors LNF was used for chondrosarcomas and soft tissue sarcomas involving bone tissues. Recycled bone was implanted as total bone, osteoarticular, or intercalary grafts, with or without prosthesis or vascularized fibular grafts. RESULTS: The 10-year graft survival rate was similar between groups, 81.8% using ECIR and 70.2% using LNF. There were no autograft-related tumor recurrences in either group. Graft survival was unrelated to type of graft or additional procedures. Complication rates tended to be higher using ECIR (64%) compared with LNF (52%) and the infection rate was significantly higher with ECIR (27%) versus LNF (0%). At the final assessment, plain radiographs revealed original recycled bone was present in 7 of 11 ECIR cases and in zero cases treated with LNF autografts, indicating that recycled bone treated with LNF autografts was remodeled into new bone. Histological examination of ECIR-treated bones revealed a delayed and incomplete endochondral ossification process, necrosis and empty lacunae. Conversely, LNF autografts showed remodeled bones with normal trabecular structures. CONCLUSIONS: ECIR and LNF treatment of autografts provided adequate tumor control with acceptable clinical results as a reconstruction method.

Prognostic value of combined psoas muscle mass and controlling nutritional status in patients with pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. METHODS: We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. RESULTS: In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). CONCLUSIONS: The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.

CD69 on Tumor-Infiltrating Cells Correlates With Neuroblastoma Suppression by Simultaneous PD-1 and PD-L1 Blockade.

INTRODUCTION: Tumor-infiltrating cells play an important role in tumor immunology, and tumor-infiltrating lymphocytes (TILs) are critical in antitumor reaction related to immune checkpoint inhibition targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). METHODS: In nude mice, which are immune deficient because they lack T cells, and inbred A/J mice, which are syngeneic to neuroblastoma cells (Neuro-2a) and have normal T cell function, we investigated the importance of T lymphocytes in immune checkpoint inhibition in mouse neuroblastoma and analyzed the immune cells in the tumor microenvironment. Then, we subcutaneously injected mouse Neuro-2ainto nude mice and A/J mice, administered anti-PD-1 and anti-PD-L1 antibodies by intraperitoneal injection, and evaluated tumor growth. At 16 d after Neuro-2a cells injection, mice were euthanized, tumors and spleens were harvested, and immune cells were analyzed by flow cytometry. RESULTS: The antibodies suppressed tumor growth in A/J but not in nude mice. The co-administration of antibodies did not affect regulatory T cells (culster of differentiation [CD]4+CD25+FoxP3+ cells) or activated CD4+ lymphocytes (expressing CD69). No changes in activated CD8+ lymphocytes (expressing CD69) were observed in spleen tissue. However, increased infiltration of activated CD8+ TILs was seen in tumors weighing less than 300 mg, and the amount of activated CD8+ TILs was negatively correlated with tumor weight. CONCLUSIONS: Our study confirms that lymphocytes are essential for the antitumor immune reaction induced by blocking PD-1/PD-L1 and raises the possibility that promoting the infiltration of activated CD8+ TIL into tumors may be an effective treatment for neuroblastoma.

Thoracoscopic removal with fluoroscopic radiographic guidance of thoracoamniotic shunting catheters in newborns.

Fetal thoracoamniotic shunting (TAS), which drains pleural effusion, is a treatment for severe primary fetal pleural effusion. While TAS is an effective treatment, its complications include bleeding and the catheter becoming dislodged, and also penetrating the thoracic cavity or chest wall. Catheters dislodged into the thoracic cavity in TAS can be removed by thoracoscopy. However, if there are adhesions in the thoracic cavity, finding the TAS catheter with a thoracoscope can be difficult. We used fluoroscopic radiography in addition to a thoracoscope to remove a TAS catheter in four patients. A 5-mm trocar was inserted into the thoracic cavity, and a 2.7-mm scope and 3-mm forceps were inserted into the trocar. We searched for TAS catheters using a thoracoscope and fluoroscopic radiography. If there are adhesions in the thoracic cavity and removing the TAS catheter is difficult, the combined use of a thoracoscope and fluoroscopic radiography may prove helpful.

Expression of programmed cell death-1 on neuroblastoma cells in TH-MYCN transgenic mice.

BACKGROUND: Immunotherapy may improve the poor prognosis of high-risk neuroblastoma. Programmed cell death-1 (PD-1) is expressed in several cancers. The tyrosine hydroxylase MYCN (TH-MYCN) transgenic mouse model is widely used in neuroblastoma research, but detailed information on its immunological background is lacking. Therefore, we studied the immunological tumor microenvironment and tumor cell surface antigen expression in homozygote and hemizygote mice and effects of antibody therapy against PD-1. METHODS: CD4, CD8, CD11b, and CD11c expression in immune cells from retroperitoneal lymph nodes and spleen was analyzed by flow cytometry. Tumor cell surface antigen expression was confirmed, and data from homozygote and hemizygote mice were compared. Effects of anti-PD-1 antibody were evaluated. RESULTS: CD4-, CD8-, CD11b-, and CD11c-positive cells were not significantly different in homozygote and hemizygote mice, and CD11b- and CD11c-positive cells were identified in the tumor microenvironment in both. Tumor cells expressed PD-1, and anti-PD-1 antibody had anti-tumor effects and significantly reduced the percentage of living tumor cells in cultures after 2 h. CONCLUSION: The immunological background is similar in homozygote and hemizygote TH-MYCN transgenic mice, and both have PD-1-positive tumor cells. Anti-PD-1 antibody suppresses tumor growth. This mouse model may be a useful for studying immunotherapy of neuroblastoma.

[Hyperammonemic encephalopathy after treatment with modified FOLFOX6 regimen for recurrent gastric cancer:a case report].

A 64-year-old female received modified FOLFOX6 therapy with continuous administration of a high concentration of 5-fluorouracil (5-FU) for recurrence of peritoneal dissemination after total gastrectomy. Twenty-nine hours after the administration, there was the sudden onset of altered consciousness and hepatic dysfunction accompanied by hyperammonemia. The consciousness and hepatic function improved the following day after treatment with branched-chain amino acid formulation, lactulose, fresh frozen plasma, and continuous hemodiafiltration. Thus, the diagnosis was 5-FU-induced hyperammonemia. Improvement of dehydration and renal dysfunction would be important for avoiding the risk of developing the side effects. Because recurrent gastric cancer is often a progressive condition, post-treatment might be promptly transferred to the other posterior regimen without 5-FU as required.

Solid-Phase Biomimetic Synthesis of Polyketide.

Solid-phase biomimetic polyketide synthesis has been developed. This method is composed of (i) carbon chain elongation of resin-bound carboxylic acid via decarboxylative Claisen condensation with malonic acid half thioester, (ii) stepwise transformation of the resulting ß-ketothioester, and (iii) hydrolysis of thioester to regenerate the carboxylic acid for the next iteration cycle. Colorimetric tests were available for convenient monitoring of the solid-phase reactions; malachite green (basic dye) and iron(III) chloride successfully detected the carboxylic acid and the ß-ketothioester, respectively. In addition, gel-phase 13C NMR could be utilized to confirm the progress of substrate immobilization. The established method was applied to the synthesis of the natural products, xylapyrone C and kavain. The present method could be further extended to the synthesis of (R)-kavain with catalytic diastereoselective asymmetric transfer hydrogenation as a key step.

Female pediatric inguinal hernia: uterine deviation toward the hernia side.

PURPOSE: We aimed to clarify the frequency and the clinical significance of deviation of the uterus in female pediatric inguinal hernia. METHODS: We retrospectively evaluated the data of 94 female pediatric inguinal hernia cases that were treated by laparoscopic percutaneous extraperitoneal closure. We assessed for correlations between uterine deviation and age, body weight, the size of the hernia orifice, and the presence of contralateral processus vaginalis (PV) patency. RESULTS: Eighty-four of 94 cases were diagnosed with unilateral inguinal hernia. A total of 62 (73.8%) of these had uterine deviation to the hernia side (Group D); 22 (26.2%) had no deviation to the hernia side (Group N) (P < 0.001). Group D cases were significantly younger than those in Group N (P = 0.0351). There was no difference in body weight, size of the hernia orifice, or contralateral PV patency between the two groups. CONCLUSION: The incidence of uterine deviation toward the hernia side was statistically significant. It is important to recognize that female pediatric inguinal hernia repair carries an increased risk of ovarian and fallopian tube damage, because these appendages are close to the hernia orifice as a result of the uterine deviation.

[Evaluation of Skeletal Muscle Mass and Functions during Perioperative Period of Breast Cancer Patients].

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass, strength and function. Sarcopenia has repeatedly been reported as a strong predictor of both short- and long-term outcomes following surgical treatment for breast cancer. In this study, 41 primary breast cancer cases who received surgery at our hospital were examined. To evaluate which factor amongst muscle volume, power or function would be most important to avoid sarcopenia after surgery, we examined muscle volume, power and function respectively. We also divided patients into groups by their ages or procedures of surgeries, then compared and analyzed within those groups. The results showed their grip power of the same side of their breast cancer and muscle volume of their legs has been decreased after surgeries. We also found patients who were equal or older than 75 years old and patients who received total mastectomy tended to lose their muscle volume or muscle power after their surgeries. These groups of patients would have potential risk to become sarcopenia after surgeries. It would be important to observe each of 3 factors, skeletal muscle volume, power and function to evaluate precisely their condition of sarcopenia. Tailor-made peri-operative rehabilitation programs, especially for elderly patients or patients who received total mastectomy, would be a possible solution to avoid sarcopenia after surgery for breast cancer.

Immune Checkpoint Inhibition Followed by Tumor Infiltration of Dendritic Cells in Murine Neuro-2a Neuroblastoma.

BACKGROUND: Most tumors responding to immunotherapy with monoclonal antibodies targeting programmed cell death protein1 (PD1) and programmed death ligand-1 (PD-L1) show surface expression of PD-L1. Neuroblastoma has been reported to show low PD-L1 surface expression. METHODS: The effect of immune checkpoint inhibitor on mouse neuroblastoma was investigated, and host immune cells were analyzed in the tumor microenvironment. Expression of co-stimulatory molecules by Neuro-2a mouse neuroblastoma cells was analyzed using flow cytometer. Neuro-2a cells were inoculated subcutaneously into A/J mice, followed by intraperitoneal injection of antibodies targeting PD-1 and PD-L1. Mice were sacrificed for the measurement of tumor weights on day 14 following tumor inoculation, and tumor-infiltrating cells were analyzed using a flow cytometer. RESULTS: Dim expression of PD-L1 was observed on the cell surface of cultured Neuro-2a cells. Growth of subcutaneous tumors was significantly suppressed, and PD-L1-expressing tumor cells were depleted by the antibody treatment. We confirmed that Neuro-2a cells opsonized by the anti-PD-L1 antibody were phagocytosed in the in vitro setting. In the treated tumor microenvironments, CD8α+ lymphocyte and CD11c+ MHC II+ cells were significantly accumulated in comparison with the control group. These CD11c+ MHC II+ cells expressed CD80, CD86, CD14, and CD40, but not CD205, PD-L1, or CTLA4. PD-1 expression was detected dimly. Immune suppressive effects of CD11b+Gr-1+ myeloid-derived suppressor cells by the administration of anti-PD-1 and PD-L1 antibodies were not observed in spleen, regional lymph nodes, or tumor microenvironment. CONCLUSIONS: Our findings raise the possibility that co-administration of anti-PD-1 and anti-PD-L1 antibodies have a synergistic effect on inhibition of tumor growth and could be an effective therapy against neuroblastoma with dim expression of PD-L1.

Poly(ester imide)s with Low Linear Coefficients of Thermal Expansion and Low Water Uptake (VIII): Structure-Flame Retardancy Relationship.

A series of ester-linked tetracarboxylic dianhydrides containing multiple para-phenylene units (TA-pPhs) was synthesized to obtain novel modified polyimides, namely poly(ester imide)s (PEsIs). The flame retardancy and film toughness of PEsIs tended to deteriorate with the structural extension of the repeating units (or monomers) via ester groups. To identify the structural factors necessary for achieving the highest flame retardancy rank (UL-94, V-0), we systematically investigated the structure-property relationships of a series of TA-pPh-based PEsIs. Among them, a PEsI derived from para-quaterphenylene-containing TA-pPh (TA-DPQP) and p-phenylenediamine (p-PDA) exhibited the best property combination, featuring an extremely high glass transition temperature (Tg), very low linear coefficient of thermal expansion (CTE), low water uptake (WA), ultralow linear coefficient of humidity (hygroscopic) expansion (CHE), unexpectedly high film toughness, and excellent flame retardancy (V-0 rank). Moreover, we examined the effects of substituents of TA-pPh and discussed the mode of action for the increased film toughness. This study also investigated the structure-property relationship for a series of PEsIs derived from isomeric naphthalene-containing tetracarboxylic dianhydrides. Some of the PEsIs obtained in this study, such as the TA-DPQP/p-PDA system, hold promise as novel high-temperature dielectric substrates for use in flexible printed circuits.

Two cases of right congenital diaphragmatic hernia with stable respiratory condition: Two case reports.

INTRODUCTION: Right congenital diaphragmatic defect (CDH) has been reported poor prognosis. However, laterality of the defect as the prognostic factor is recent controversial topic. We experienced two cases of right CDH with relatively stable respiratory condition and good clinical course. PRESENTATION OF CASES: Case 1 was a girl diagnosed with right CDH by fetal ultrasonography and delivered by planned caesarian section at 37 weeks, 3 days. Fetal MRI showed liver herniation into the right thoracic cavity. High frequency oscillatory ventilation with nitric oxide gas was administered until day 5. At surgery on day 8, we found defects in the right posterolateral diaphragm and sac herniation of the right side of the liver into the right thoracic cavity. The postsurgical course was uneventful, and she was discharged on day 41. Case 2 was a girl with suspected congenital jejunal atresia after fetal ultrasonography detected polyhydramnios and dilatation. She was delivered by normal vaginal delivery at 38 weeks, 5 days, and thoraco-abdominal X ray showed right CDH but no small intestinal atresia. Surgery performed on day 3 found liver herniation into the diaphragmatic defect. Subsequently, bacterial infection occurred and was treated with the antibiotics, but her respiratory condition remained stable. She was discharged on day 49. DISCUSSION: The volume of herniated abdominal organs is affected by the presence of a hernia sac or the size of the diaphragmatic defect. CONCLUSION: The size of diaphragmatic defect, but not the laterality of the diaphragmatic defect, may be an important prognostic factor in right CDH.

A rare case of extremely low birth weight infant with Beckwith-Wiedemann syndrome.

INTRODUCTION: Beckwith-Wiedemann syndrome (BWS) manifests distinctive features, such as macroglossia, overgrowth, and abdominal wall defects. In this report, we describe a case of BWS in an extremely low birth weight infant diagnosed at three months after birth because of the intensive care for low birth weight. PRESENTATION OF CASE: A female infant was delivered at 24 weeks and 6 days of gestation with a weight of 845 g. After birth, significant small intestinal intra-umbilical prolapse was observed, and abdominal wall closure using a sutureless method was performed on day zero. Careful neonatal management was performed; however, an episode of bloody stools led to a diagnosis of intestinal volvulus due to intestinal malrotation. At 119 days of age, the Ladd procedure was performed. Notably, during anaesthesia induction, features suggestive of BWS were observed, leading to its diagnosis. DISCUSSION: Early diagnosis of BWS is vital because of its association with tumors. However, because she was an extremely low birth weight infant who required oral intubation and supine management for respiratory control, nevus flammeus and macroglossia were not observed. Therefore, BWS was not diagnosed for approximately three months after birth. It is important to recognize that omphalocele in extremely low birth weight infants is a risk factor for delayed diagnosis of BWS. CONCLUSION: Timely diagnosis of BWS is critical because of its association with tumors and varied clinical presentations. Early screening, especially for tumors, and awareness among surgical practitioners can aid in timely interventions and improved patient outcomes.

A rare case of oesophageal atresia complicated by duodenal atresia and anorectal malformation successfully treated with multi-stage surgery.

INTRODUCTION: Oesophageal atresia, duodenal atresia, and anorectal malformations are rare. This report describes a case of an infant with these three conditions treated using a multi-stage surgical procedure. PRESENTATION OF CASE: A male infant was delivered via caesarean section at 34 weeks and 4 days of gestation, weighing 1709 g. Radiography at birth showed a coil-up of the gastrointestinal tube in the oesophagus, a double bubble sign; the patient was subsequently diagnosed with gross type C oesophageal atresia with duodenal atresia. A gastrostomy was performed at day 0. Oesophago-oesophageal anastomosis was performed after tracheoesophageal fistula and blind-end dissection. A duodeno-duodenal diamond-shaped anastomosis was performed, and a tube enterostomy was created from the gastric area near gastrostomy as a trans-anastomotic feeding tube. A colostomy was performed in the descending colon owing to a non-rotation-type anomaly of intestinal malrotation. After other multi-stage surgeries and weight gain, posterior sagittal anorectoplasty was performed at age 1 year 2 months. DISCUSSION: Triple atresia (TA), characterized by triumvirate oesophageal atresia, duodenal atresia, and anorectal malformations, remains a clinical puzzle. Notably, standardized therapeutic guidelines for managing TA are lacking. The complexity of this constellation of anomalies necessitates astute diagnostic acumen and strategic treatment planning. CONCLUSION: Our patient showed a favourable clinical course with an accurate and timely diagnosis, serving as an experience for an innovative multi-stage therapeutic strategy. Our case showed the appropriate challenges of TA while illuminating the potential for successful outcomes through meticulous clinical management.

Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report.

BACKGROUND: Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage. CASE PRESENTATION: A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful. CONCLUSION: We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.

Exhaustion, rather than lack of infiltration and persistence, of CAR-T cells hampers the efficacy of CAR-T therapy in an orthotopic PDAC xenograft model.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated impressive success in the treatment of patients with hematologic tumors yet achieved very limited efficacy for solid tumors due to hurdles unique to solid tumors. It is also noted that the tumor microenvironment composition varies between tumor type, which again imposes unique set of hurdles in each solid tumor. Therefore, elucidation of individual hurdles is key to achieving successful CAR-T therapy for solid tumors. In the present study, we employed an orthotopic human PDAC xenograft model, in which quantitative, spatial and functional dynamics of CAR-T cells in tumor tissues were analyzed to obtain insights into ways of overcoming PDAC related hurdles. Contrary to previous studies that demonstrated a limited persistency and infiltration of CAR-T cells in many solid tumors, they persist and accumulated in PDAC tumor tissues. Ex vivo analysis revealed that CAR-T cells that had been recovered at different time points from mice bearing an orthotopic PDAC tumor exhibited a gradual loss of tumor reactivity. This loss of tumor reactivity of CAR-T cells was associated with the increased expression of AMP-activated protein kinase and Mitofusin 1/ Dynamin-related protein 1 ratio.

Neonatal inguinal hernias containing the uterus: a case report on changes in uterine position.

A female newborn weighing 542 g and delivered at 27 weeks gestation presented with bilateral inguinal hernias while in the neonatal intensive care unit. Ultrasonography confirmed herniation of the uterus into the right inguinal hernia without signs of incarceration. Due to the absence of complications, she was discharged and scheduled for follow-up at the outpatient clinic. At 11 months of age, a subsequent ultrasonography showed only omental herniation, with no evidence of uterine prolapse. When she reached 1 year of age, a laparoscopic percutaneous extraperitoneal closure procedure was performed. During the surgery, it was observed that the uterus and fallopian tubes were located near the hernia orifice, but no clear prolapse was detected. The procedure concluded safely with successful high ligation. It has noted that in cases of uterine prolapse hernias, the uterus tends to recede as the child grows, which supports the decision to delay surgery for improved safety.

Metastatic lung tumor from hepatocellular carcinoma with tumor thrombus invasion in the pulmonary vein: a case report.

BACKGROUND: Metastatic lung tumor with a tumor thrombus in the peripheral pulmonary vein is very rare. We present a case of a metastatic lung tumor from hepatocellular carcinoma (HCC) with tumor thrombus invasion in the pulmonary vein that was diagnosed preoperatively and underwent complete resection by segmentectomy. CASE PRESENTATION: A 77-year-old man underwent laparoscopic lateral segment hepatectomy for HCC eight years ago. Protein induced by vitamin K absence or antagonist-II remained elevated from two years ago. Contrast-enhanced chest computed-tomography (CT) showed a 27 mm nodule in the right apical segment (S1). He was pathologically diagnosed with a metastatic lung tumor from HCC via transbronchoscopic biopsy. We planned to perform right S1 segmentectomy. Before surgery, contrast-enhanced CT in the pulmonary vessels phase for three-dimensional reconstruction showed that the tumor extended into the adjusting peripheral pulmonary vein, and we diagnosed tumor thrombus invasion in V1a. The surgery was conducted under 3-port video-assisted thoracic surgery. First, V1 was ligated and cut. A1 and B1 were cut. The intersegmental plane was cut with mechanical staplers. Pathological examination revealed moderately-differentiated metastatic HCC with tumor thrombus invasions in many pulmonary veins, including V1a. No additional postoperative treatments were performed. CONCLUSIONS: As malignant tumors tend to develop a tumor thrombus in the primary tumor, it might be necessary to perform contrast-enhanced CT in the pulmonary vessel phase to check for a tumor thrombus before the operation for metastatic lung tumors.

Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells.

Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.