[Two Cases of Stage â £ Occult Breast Cancer].

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

[A Case of Breast Metastasis of Gastric Cancer after an Eight Year Latency Period].

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

[Incidence of Catheter-Related Thrombosis in Patients with Long-Term Indwelling Central Venous Port Who Received Chemotherapies for Unresectable Advanced Digestive Cancers].

BACKGROUND: Most patients with unresectable advanced digestive cancers require placement of a fully implantable venous access port to facilitate safe delivery of anti-cancer drugs. Anti-VEGF therapies are commonly used even though they increase the risk of thrombosis. The objective of this study was to assess the incidence of radiologically confirmed catheter-related thrombosis(CRT)in patients with advanced digestive cancers. METHODS: We retrospectively reviewed 88 patients with advanced digestive cancers who had adapted implantable ports placed in our institution for chemotherapy. RESULTS: Thirty-nine patients were diagnosed with colorectal cancer, 26 with gastric cancer, 12 with pancreatic cancer, 8 with esophageal cancer, and 3 with other cancers. During follow-up, 22 patients(25%)received anti-VEGF therapies, while 66 patients(75%)did not. Four out of 88 patients(4.5%)had asymptomatic CRT. The incidence of CRT was the same(4.5%)regardless of whether the patient received anti-VEGF therapy. CONCLUSIONS: In patients with digestive cancers who had implantable venous access ports, the incidence of the CRT was 4.5% with no association with anti-VEGF therapies.

[A Case of Long-Term Survival after Para-Aortic Lymph Node Recurrence Following the Curative Resection of Gastric Cancer Treated Using Multimodality Therapy Including Salvage Surgery].

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

Cetuximab retreatment in patients with metastatic colorectal cancer who exhibited a clinical benefit in response to prior cetuximab: A retrospective study.

Clinical benefits of cetuximab retreatment in patients with metastatic colorectal (mCRC) have been reported. In the present study, the effect of cetuximab retreatment on predictive markers was investigated by evaluating the clinical benefit of initial cetuximab treatment prior to cetuximab retreatment. Between November 2012 and March 2017, 14 patients with KRAS proto-oncogene GTPase exon 2 wild-type mCRC who exhibited a clinical benefit (confirmed stable disease for at least 6 months or a clinical response) to an initial cetuximab-based regimen, who received multiple lines of chemotherapy following disease progression and ultimately received a second cetuximab and irinotecan regimen, were retrospectively analyzed. For retreatment, patients received bi-weekly irinotecan (120-150 mg/m2) combined with cetuximab (400 mg/m2 as an initial dose, followed by 250 mg/m2, weekly). The median age of the 14 patients (11 males, 3 females) was 68 years (32-77). The median progression-free survival (PFS) following prior cetuximab-based therapy was 6.6 months (range, 4.1-18.4). Initial cetuximab treatment was administered as a first-line treatment in 11 patients, a second-line treatment in 1 patient and a third-line treatment in 2 patients. The median interval time between the last cycle of initial cetuximab-based therapy and the first cycle of cetuximab retreatment was 13.1 months (range, 6.0-37.1). The objective response rate of cetuximab retreatment was 21.4% and the median PFS was 4.4 months (95% confidence interval, 1.4-5.6). The Spearman's correlation coefficient for the PFS following retreatment and duration of initial cetuximab-based regimens demonstrated a more marked correlation compared with that between the PFS following retreatment and the interval time between the two regimens (r=0.45, P=0.11 vs. r=0.08, P=0.79). Cetuximab retreatment may provide clinical benefit to patients with mCRC who were good responders with longer periods of initial cetuximab-based therapy.

[A Case of Primary Spinddle Cell Carcinoma of the Breast].

A 76-year-old female underwent breast-conserving surgery of the right breast and sentinel lymph node biopsy for primary breast cancer. Three years later, mammography and ultrasonography showed a small nodule in the right breast. There was nothing abnormal in the left breast. Three months later, she complained of a huge and rapid growing mass in the left breast. Malignant cells were obtained on fine needle aspiration biopsy in the right breast tumor. But it was not possible to diagnose whether the left breast tumor was benign or malignant on fine needle aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node biopsy of the right side were performed. Pathological diagnosis were squamous cell carcinoma of the right breast and spindle cell carcinoma of the left breast. Although the patient was treated with adjuvant chemotherapy, she had an early relapse with pleural, lung and bone metastases. The patient died approximately 8 months after operation. Spindle cell carcinoma presents many problems about therapy and prognosis. Further accumulation analysis is necessary.

[A Case of Primary Acinic Cell Carcinoma(ACC)of the Breast].

A49 -year-old woman presented with a 3.5 cm mass in her right breast. Mammography revealed a lobular mass with poorly defined margins and no microcalcification. Ultrasonography showed a hypoechoic mass with an irregular margin. The tumor was diagnosed as breast carcinoma using a core needle biopsy. The patient underwent a modified radical mastectomy with sentinel lymph node biopsy, and received adjuvant chemotherapy. The tumor consisted of 2 types of carcinoma. The center of the tumor was solid-tubular carcinoma, and the periphery was acinic cell carcinoma(ACC). Histopathologically, the neoplastic cells of the periphery were characterized by widespread acinic cell-like differentiation with a eosinophilic granular or clear cytoplasm, resembling acinic cells of the parotid gland(t3, f[+], ly0, v0, n0, stage II B). Immunohistochemically, the specimens tested positive for salivary gland amylase, and negative for collagen type IV , ER, PgR, and HER2. We administered UFT as adjuvant chemotherapy. Eight months after surgery, local recurrence was observed. ACC of the breast is rare, and has been reported to have a good prognosis. Further investigations are needed to elucidate its true histogenesis the appropriate treatment.

[A Case of Mediastinal Dissection by Video-Assisted Thoracoscopic Surgery (VATS)in a Patient with Mediastinal Nodal Recurrence from Thyroid Carcinoma after Primary Surgery via Median Sternotomy].

A70 's male was diagnosed with advanced papillary thyroid carcinoma and underwent total thyroidectomy with left lymph node dissection(T4a, N1b, M0, stage IV A). Six years after the surgery, subclavicular and mediastinal lymph node recurrence was observed. Radioiodine therapy was not successful for those lesions. Lymph node dissection was performed via the cervical and transsternal approaches. One year after the second surgery, cervical and mediastinal lymph node recurrence was again observed. We removed the cervical lymph nodes via the cervical approach. One month after cervical dissection, we removed the mediastinal lymph nodes via video-assisted thoracoscopic surgery(VATS). The lymph nodes were relatively easily dissected by VATS under excellent surgical views. Repeat mediastinal dissection via median sternotomy could be associated with significant complications. VATS is expected to reduce the risk of reoperation and enhance surgical outcomes.

[A Case of Minimal Thyroid Carcinoma Diagnosed by a Solitary Pulmonary Metastasis].

We report a case of minimal thyroid carcinoma diagnosed by a solitary pulmonary metastasis. A 70's man visited a medical practitioner because of chest discomfort, and there was an abnormality on the chest X-ray. Chest computed tomography(CT) showed a nodule in the right middle lobe of the lung. Positron emission tomography with 18-fluorodeoxyglucose(FDG)-PET revealed increased FDG uptake in that tumor, but did not reveal any other lesion. The tumor was clinically suspected to be a carcinoid tumor, primary lung cancer, metastatic lung cancer, or a benign tumor. Right middle lobe lobectomy was performed, and the tumor was diagnosed as a metastasis from a thyroid papillary carcinoma by pathological diagnosis during surgery. After surgery, we found a tumor in the left lobe of the thyroid by CT and US. Because the patient did not desire 131I therapy, he underwent a left hemithyroidectomy and neck dissection. There was a papillary carcinoma 1.0 cm in the thyroid gland and there were 3 cervical lymph node metastases. There has been no recurrence for 11 years after surgery.

Early Growth Response-1 Plays an Important Role in Ischemia-Reperfusion Injury in Lung Transplants by Regulating Polymorphonuclear Neutrophil Infiltration.

BACKGROUND: Early growth response-1 (Egr-1) has been shown to be a trigger-switch transcription factor that is involved in lung ischemia-reperfusion injury (IRI). METHODS: Mouse lung transplants were performed in wild-type (WT) C57BL/6 and Egr1-knockout (KO) mice in the following donor → recipient combinations: WT → WT, KO → WT, WT → KO, and KO → KO to determine whether the presence of Egr-1 in the donor or recipient is the most critical factor for IRI. Pulmonary grafts were retrieved after 18 hours of ischemia after 4 hours of reperfusion. We analyzed graft function by analyzing arterial blood gas and histology in each combination and assessed the effects of Egr1 depletion on inflammatory cytokines that are regulated by Egr-1 as well on polymorphonuclear neutrophil (PMN) infiltration. RESULTS: Deletion of Egr1 improved pulmonary graft function in the following order of donor → recipient combinations: WT → WT < WT → KO < KO → WT < KO → KO. Polymerase chain reaction assays for Il1B, Il6, Mcp1, Mip2, Icam1, and Cox2 showed significantly lower expression levels in the KO → KO group than in the other groups. Immunohistochemistry demonstrated clear Egr-1 expression in the nuclei of pulmonary artery endothelial cells and PMN cytoplasm in the WT grafts. Flow cytometry analysis showed that Egr1 deletion reduced PMN infiltration and that the extent of reduction correlated with graft function. CONCLUSIONS: Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributed more to this phenomenon through regulation of PMN infiltration. Donor Egr-1 expression in pulmonary artery endothelial cells may play an important role in PMN infiltration, which results in IRI after lung transplantation.

[Repair of a huge Bochdalek hernia by direct suture and mesh reconstruction].

A 72-year-old man presented with complaints of sudden abdominal pain and vomiting. After a thorough examination, the patient was diagnosed with a left-sided Bochdalek hernia with strangulation of the stomach and spleen. The impaction was cleared by drainage of the stomach contents by a nasogastric tube;then, surgical repair through thoracic approach was performed. The herinia port size was large, and the defect of diaphragm was successfully repaired by both direct closure and mesh reconstruction.

[A case of bone marrow carcinomatosis with disseminated intravascular coagulation arising from breast cancer successfully treated with paclitaxel plus bevacizumab].

We report a case of bone marrow carcinomatosis with disseminated intravascular coagulation (DIC) originating from metastatic breast cancer that was treated with paclitaxel plus bevacizumab. A woman in her 30s was diagnosed with bone marrow carcinomatosis arising from metastatic breast cancer 2 years previously. Pathologically, estrogen receptor (ER) and progesterone receptor(PgR) / -positive and human epidermal growth factor receptor 2(HER2/neu)-negative scirrhous carcinoma was diagnosed. She improved after treatment with paclitaxel plus bevacizumab and zoledronic acid. Subsequently, she was treated with hormonal therapy(tamoxifen plus luteinizing-hormone-releasing hormone [LH-RH]agonist) for 7 months. Because progressive bone metastasis was identified and tumor markers increased, the patient was administered paclitaxel plus bevacizumab again. Fifteen days after chemotherapy was initiated, DIC developed. Chemotherapy was continued without decreasing the dose, and recombinant human soluble thrombomodulin (rTM) was added. The DIC resolved in 5 days. After 6 courses of paclitaxel plus bevacizumab, improvement of tumor markers and bone metastasis was observed. Paclitaxel plus bevacizumab can be effective for treatment of bone marrow carcinomatosis with DIC originating from metastatic breast cancer.

Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model.

OBJECTIVES: Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection. METHODS: Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft. RESULTS: Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1ß), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1ß and MCP-1 mRNA (P < 0.05). CONCLUSIONS: Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death.

BACKGROUND: Although lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia-reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI. METHODS: Cold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion. RESULTS: Only the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group. CONCLUSIONS: This study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD.

Effect of donor pre-mortem hypoxia and hypotension on graft function and start of warm ischemia in donation after cardiac death lung transplantation.

BACKGROUND: The start of warm ischemic time (WIT) of donor lungs in donation after cardiac death (DCD) is not clearly defined. We investigated the effect of donor pre-mortem hypotension and hypoxia to determine which physiologic factor is the determinant of WIT onset in controlled DCD lung transplantation. METHODS: Twenty mechanically-ventilated donor pigs were placed in 4 groups (n = 5 each) and exposed to each of the pseudo-agonal conditions for 60 minutes: (1) control group, no intervention and optimum ventilation, followed by cardiac arrest; (2) hypotension (HT) group, controlled cardiac tamponade reducing systolic blood pressure to <50 mm Hg, followed by cardiac arrest; (3) hypoventilation (HV) group, ventilation with room air at 5 breaths/min, followed by cardiac arrest; (4) non-circulation (NC) group, initial cardiac arrest, followed by a 60-minute standoff time. The lung graft was retrieved and the left lung was transplanted to the recipient. Graft function was evaluated for 4 hours after contralateral pulmonary artery ligation. The reperfusion injury was evaluated based on tissue cytokine expression, wet weight-to-dry weight ratio, and histology at the end of the reperfusion period. RESULTS: Impaired post-transplant graft function was seen in the HV group, which had significantly poorer oxygenation during the reperfusion period than the other groups (p < 0.001). The HV group also had higher tissue levels of interleukin-8 (p < 0.05), a higher wet weight-to-dry weight ratio (p < 0.05), and histologic findings of graft tissue injury than the control group. The difference in these parameters among the control, HT, and NC groups was not significant. CONCLUSIONS: Only pre-mortem hypoxia provoked by hypoventilation significantly impaired lung graft function in DCD lung transplantation. Ventilatory rather than circulatory deterioration can trigger the onset of warm ischemia.

Suppression of inflammatory cytokines during ex vivo lung perfusion with an adsorbent membrane.

BACKGROUND: Lung grafts can be perfused ex vivo for 2 hours without edema formation; however, prolonged ex vivo lung perfusion (EVLP) eventually induces lung injury. This study evaluated the change in proinflammatory cytokines of the perfusate during EVLP and investigated the effect of cytokine removal using an adsorbent membrane. METHODS: Porcine heart-lung blocks were harvested after electrically induced cardiac arrest and underwent 12-hour EVLP with an adsorbent membrane (membrane group: n = 5) and without an adsorbent membrane (control group: n = 6). RESULTS: In the control group, both tumor necrosis factor-alpha and interleukin 8 levels were elevated in the perfusate 2 hours after perfusion. Although tumor necrosis factor-alpha and interleukin 8 levels were significantly lower in the membrane group than in the control group during the EVLP period, there was no significant difference in oxygenation, pulmonary vascular resistance, edema formation, or myeloperoxidase activity between the two groups. CONCLUSIONS: Tumor necrosis factor-alpha and interleukin 8 levels of the perfusate were elevated during EVLP. Although adverse effects of these inflammatory cytokines were anticipated, removal of inflammatory cytokines by the adsorbent membrane did not improve lung function during prolonged EVLP. Factors other than the cytokines may play a major role in causing lung injury during EVLP. Further research is needed to investigate the real mechanism of lung graft injury during prolonged EVLP and to establish longer EVLP duration for graft treatment. This strategy could contribute to the salvage of potentially damaged lungs, especially from cardiac death donors, and to expansion of the donor pool.

Recurrent lung cancer in the mediastinum noticed after a living-donor lobar lung transplantation.

We describe a case of lung cancer in a living-donor lobar lung transplantation (LDLLT) recipient that was identified because of a recurrence in the mediastinum. The patient was a 55-year-old woman who had undergone bilateral LDLLT for nonspecific interstitial pneumonia. She developed dyspnea upon exertion at 15 months after transplantation and was diagnosed as suffering from chronic rejection. A computed tomography scan also revealed enlarged mediastinal lymph nodes (LNs) that were subsequently confirmed as poorly differentiated squamous cell carcinomas. Retrospectively, a small tumor was found in the explanted right lung tissue, the microscopic findings of which were similar to those of the mediastinal lesion. A whole body examination revealed no other lesions; thus we resected the LNs and subsequently irradiated the mediastinum. Recurrent disease appeared in her transplanted lungs 10 months after resection of the LNs, and she died of pneumonia with chronic rejection 2 years and 7 months after transplantation.

[Feasibility and anti-tumor activity of postoperative adjuvant chemotherapy with gemcitabine for resected pancreatic cancer].

The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and June 2007, patients with resected invasive pancreatic cancer (stage III, IVa, IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not receive chemotherapy (n=11). Started the administration of GEM 38.5 days after surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was not observed in the GEM group. There was a significant difference in overall survival between the GEM group and the no-chemotherapy group (p=0.037), but there was no significant difference in disease-free survival between the two groups. Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with invasive pancreatic cancer.

[Two cases of advanced low rectal cancer, preoperative chemo-radiation therapy leading to complete histological response].

We report two cases of advanced low rectal cancer, with preoperative chemo-radiation therapy leading to a complete histological response. Case 1 was a 74-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was performed. Then, 30 days after chemo-radiation, we conducted a low anterior resection with lymph node dissection. Histological examination revealed no residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was performed. 28 days after chemo-radiation, we conducted an abdominoperineal resection with lymph node dissection and a partial resection of the liver. Histological examination revealed well-differentiated adenocarcinoma in the resected liver tissue, but a rectal tumor was replaced by scar tissue with no viable cells.