[Paclitaxel plus Bevacizumab Combination Therapy for Esophageal Metastasis of Breast Cancer-A Case Report].

An 80-year-old woman with a history of left breast cancer complained of dysphagia. At the age of 67 years, she had undergone a left modified radical mastectomy, chemotherapy, and endocrine therapy for left breast cancer. Six years after adjuvant therapy completion, she developed dysphagia. Chest CT showed only midesophageal stenosis. Endoscopic examination revealed whole circumferential stenosis without mucosal abnormality located 25 cm from the incisors, and a biopsy showed histologically normal mucosa. Endoscopic balloon dilatation was performed 5 times in 1 year and 3 months. Subsequently, a biopsy specimen revealed adenocarcinoma, which suggested metastasis from the previous breast cancer. One month after the initiation of tamoxifen administration, dyspnea due to pleural effusion was encountered. We treated this via pleural adhesion therapy and changed the treatment to paclitaxel plus bevacizumab combination therapy. She continued paclitaxel plus bevacizumab therapy for 1 year and 4 months without any signs of recurrence.

Boerhaave syndrome presenting black pleural effusion: A case report.

A 55-year-old man experienced nausea and vomiting after brushing his teeth. He experienced back pain after this episode and visited our emergency department. Chest computed tomography (CT) images revealed moderate pleural fluid accumulation and mild left pneumothorax. Thoracentesis showed black pleural effusion. Thoracic drainage included food debris with black pleural effusion, and gastroscopy revealed food debris and perforation of the lower esophagus. Esophageal perforation was surgically repaired using omental implantation and pleuroclysis. Given the high mortality rate associated with black pleural effusion, prompt diagnostic procedures and corresponding management are essential.

[Case of Unresectable Gastric Mixed Neuroendocrine Neoplasm(MiNEN)Treated with Chemotherapy].

A 68-year-old man diagnosed with gastric mixed neuroendocrine-non-neuroendocrine neoplasia(MiNEN)concomitant with liver metastasis received chemotherapy using ramucirumab and paclitaxel. A decrease in tumor marker levels and size of the metastatic liver lesions was observed after 3 courses of treatment. However, the patient developed progressive disease after 9 courses of chemotherapy; hence, nivolumab chemotherapy was initiated. Although liver metastases were reduced after 2 courses of nivolumab, the patient developed new liver lesions after 18 courses of treatment; irinotecan, S-1 and oxaliplatin, and trifluridine/tipiracil were then administered. Liver metastases progressed despite changing the regimen, and the patient died 25 months after the initiation of chemotherapy. Gastric MiNEN usually shows poor prognosis, and there is lack of consensus regarding optimal treatment. Ramucirumab and nivolumab are relatively well-tolerated and may be effective for chemotherapy.

[Change in Therapy for Malignant Pleural Mesothelioma at Our Hospital].

When molecular target drug began to be used for chemotherapy to treat malignant pleural mesothelioma in 2014, we introduced this treatment strategy for 61 patients who were diagnosed and were being treated in our hospital. Chemotherapy was performed on 37 patients, while 12 patients underwent surgical remedy and best supportive care was provided to another 12 patients. Molecular target drug was used as the primary chemotherapy treatment in 14 cases, while it was the secondary treatment in 22 others. Pleural decortication was performed as the operative method for all the 12 cases requiring surgical remedy, and 2 of these cases were shifted to extrapleural pneumonectomy. By the chemotherapy, there were many cases of PS≥2, non‒epithelial type, advanced stage, LMR<2.74 of the biomarker. When we compared surgical remedy with the chemotherapy clinicopathologically. In the prognostic examination, in median survival time of all cases, as for 23 months, the chemotherapy, 31 months, the surgical remedy was not reached. Prognostic improvement of stage ⅢA was determined according to the stage of the chemotherapy. A multivariate variable analysis revealed that only a non‒sarcomatous type was a good prognostic factor, and surgery remedy was not.

[A Case of Intraductal Apocrine Carcinoma of the Breast].

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

[A Case of Metastatic Pancreatic Ductal Adenocarcinoma Successfully Treated with Modified FOLFIRINOX and Concurrent Radiotherapy].

A 70-year-old man with metastatic pancreatic ductal adenocarcinoma(cT4N1bM1, cStage Ⅳ)underwent chemotherapy with modified FOLFIRINOX without any severe adverse event to 20 cycles. In the middle of that, concurrent irradiation toward primary lesion(total dose, 43.2 Gy)was administered. Grade 1 adverse events include anemia, thrombocytopenia, hypoalbuminemia, hypokalemia, alkaline phosphatase increased, hypertension, peripheral sensory neuropathy, fatigue, anorexia and nausea. The relative dose intensities of oxaliplatin, irinotecan and fluorouracil at 6 months after beginning of treatment were 77.6, 84.0 and 88.3 percent, respectively. The total dose of administered oxaliplatin was 825 mg to the square meter. The primary lesion had been stable for the 20 cycles, although peritoneal dissemination had progressively increased in size. For 17 months, opioid was not necessary for the control of abdominal or back pain to the end of third-line treatment. Though safety or clinical benefits of modified FOLFIRINOX plus concurrent radiotherapy for metastatic pancreatic ductal adenocarcinoma have not been reported, in this case, such treatment might contribute to prolong prognosis or prevent developing abdominal or back pain.

[A Case of Malignant Thyroid Lymphoma That Was Difficult to Differentiate from Methotrexate-Associated Lymphoproliferative Disorders(MTX-LPD)].

A female patient in her 60s was going to get treatment for rheumatoid arthritis(RA). Considering the possibility of using biologics, CT examination was performed for screening of malignant diseases. A mass shadow in the left lobe of the thyroid gland was detected. The patient was followed up, and ultrasonography did not reveal any malignant findings. She was treated with methotrexate(MTX), and 1 year later, the thyroid mass was enlarged on CT. Ultrasonography revealed an enlarged hypoechoic region. Fine needle aspiration cytology revealed malignant lymphoma. Excisional biopsy was performed to determine the treatment plan. The pathological diagnosis was follicular lymphoma, and the possibility of methotrexate- associated lymphoproliferative disorders(MTX-LPD)persisted. It was difficult to discontinue MTX because of the high activity of RA. She was treated with rituximab for malignant lymphoma and concurrently with MTX for RA. The thyroid tumor disappeared for 3 months. Four years later, there is no sign of tumor recurrence.

Very delayed liver metastasis from small bowel gastrointestinal stromal tumor (32 years after resection of the small bowel GIST): Report of a case.

INTRODUCTION: Recurrent forms of gastrointestinal stromal tumor (GIST) include liver metastases and peritoneal dissemination. Recurrence often occurs within 2 years. We report a case of liver metastasis, which was detected 30 years after resection of a primary lesion in the small intestine and was resected 32 years later. PRESENTATION OF CASE: The patient was a 72-year-old woman and was being followed up for ureteral stones at the department of urology of our hospital. Computed tomography (CT) showed a small mass in segment 7 of the liver, 2 years ago. As the tumor gradually increased, a biopsy was performed, and a mesenchymal tumor was diagnosed. The tumor continued to increase in size and partial hepatectomy was performed. GIST was suspected from the sample extracted during hepatectomy. The patient had undergone a resection of the small intestine for a tumor 32 years ago. On tracing her medical records, it was confirmed that resection of the small intestine was performed for the diagnosis of leiomyosarcoma. DISCUSSION: Based on the block specimen from 32 years ago, the tumor of the intestine was confirmed to be GIST, and the liver mass was finally diagnosed as liver metastasis of the GIST that had occurred 32 years ago. CONCLUSION: We experienced a case of liver metastasis 32 years after surgery for the first small intestinal GIST. To the best of our knowledge, this case had the longest disease-free interval before metastasis to the liver.

[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.

RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer.

PURPOSE: Several trials have evaluated the efficacy of rechallenge treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS: We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS: Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION: RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.

[A Case of Unresectable Intrahepatic Cholangiocarcinoma Successfully Treated with Chemoradiotherapy].

A 69-year-old woman with unresectable intrahepatic cholangiocarcinoma(T3N1M1, Stage Ⅳ)underwent chemoradiotherapy with gemcitabine, cisplatin and irradiation toward primary lesion(total dose, 36 Gy). Grade 3 or 4 adverse events include leukopenia, neutropenia, and anemia. The relative dose intensities at 6 months after beginning of treatment were 58.9%(gemcitabine)and 80.2%(cisplatin), respectively. The total dose of administered cisplatin was 525 mg to the square meter. Partial response was obtained, and after that, the representative lesions have been stable with continuous administration of gemcitabine. As some studies have reported clinical benefits of chemoradiotherapy for unresectable intrahepatic cholangiocarcinoma, further clinical investigations are expected.

Frequency-Multiplexed Photon Pairs Over 1000 Modes from a Quadratic Nonlinear Optical Waveguide Resonator with a Singly Resonant Configuration.

We demonstrate a frequency multiplexed photon pair generation based on a quadratic nonlinear optical waveguide inside a cavity which confines only signal photons without confining idler photons and the pump light. We monolithically constructed the photon pair generator by a periodically poled lithium niobate (PPLN) waveguide with a high reflective coating for the signal photons around 1600 nm and with antireflective coatings for the idler photons around 1520 nm and the pump light at 780 nm at the end faces of the PPLN waveguide. We observed a comblike photon pair generation with a mode spacing of the free spectral range of the cavity. Unlike the conventional multiple resonant photon pair generation experiments, the photon pair generation was incessant within a range of 80 nm without missing teeth due to a mismatch of the energy conservation and the cavity resonance condition of the photons, resulting in over 1000-mode frequency multiplexed photon pairs in this range.

[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.