[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer( invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

[A Case of Recurrent Breast Cancer with Multiple Bone Metastasis Effectively Treated by CDK4/6 Inhibitor in Addition to Aromatase Inhibitor].

We report a case of recurrent breast cancer with multiple bone metastasis in a 62-year-old woman. Her breast cancer (invasive ductal carcinoma, T2N0M0, Stage ⅡA)was resected in 2001(partial mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(UFT)and irradiation to her left remnant breast. In February 2018, she complained of severe pain in right femoral joint and hip. CT scan showed a left cystic breast tumor(17 cm)and multiple bone metastasis. The core needle biopsy of the costal bone lesion and left mastectomy were performed. These pathological findings were recurrence of the breast cancer(ER+). The endocrine therapy(exemestane, aromatase inhibitor), the administration of denosumab and irradiation to painful bone lesions were performed, but it did not suppress tumor progression. The treatment of letrozole plus palbociclib(CDK4/6 inhibitor)were continued for 3 months from May 2018, and this therapy made her bone lesions smaller, but palbociclib were stopped due to its severe neutropenia. After that, the single administration of letrozole was continued, but the tumor marker did not become normal. In February 2019, abemaciclib was administered in addition to letrozole. One year later, her symptoms improved and her bone metastases have showed partial response.

[A Useful Method of Nipple-Side HydroMARK-Marking before Neoadjuvant Chemotherapy in the Breast Preserving Surgery-A Case Report with pCR of the Triple Negative Breast Cancer].

When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).

[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].

We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.

[Fluorescence Detection System for Intraoperative Identification of the Parathyroid Glands in a Patient with Thyroid Cancer with a Right Non-Recurrent Inferior Laryngeal Nerve].

Intraoperative identification of the parathyroid gland is very important during thyroid and parathyroid surgery.Recently, intrinsic fluorescence of the parathyroid gland was identified and reported.We report the case of a 45-year-old woman with thyroid papillary cancer.Before surgery, neck and chest CT showed a thyroid tumor(20mm)of the right lobe and an aberrant right subclavian artery.Her thyroid cancer(T1N1M0, Stage Ⅰ)was resected in December 2017(right lobectomy and lymph node dissection).During surgery, her parathyroid glands were visually inspected by the surgeon as well as by a ready-made photodynamic eye(PDE-neo)system.Diagnosis was performed using the intraoperative fast pathological method.Her inferior laryngeal nerve was non-recurrent(Toniato ⅡA).This photodynamic eye(PDE-neo)system is an effective and useful method that decreases the operation time and enables faster detection of the parathyroid gland.

[A Case Report of Recurrent Bleeding and Massive Malodorous Effusion Due to Skin Invasion of Advanced Breast Cancer Successfully Treated with Mohs' Paste].

We report a case involving a 65-year-old woman with skin invasion and destruction by left large breast cancer(T4cN0M0, Stage ⅢB). She had severe anemia with recurrent bleeding on the cancer surface and needed blood transfusion, and massive malodorous effusion from the skin lesion resulted in hypoalbuminemia and recurrent bacteremia. Metronidazole gel treatment for malodorous effusion and postmenopausal hormonal therapy were administered at first. After using Mohs' paste 4 times with 1- or 2-week intervals, the bleeding and effusion stopped, and the primary cancer tumor almost disappeared. Bacteremia also improved with antibiotics, and amelioration of distress was observed. Following this, systemic chemotherapy was performed. Mohs' paste was a very useful method for symptom management of malignant skin lesions with bleeding and massive effusion.

[A Case Report of Continuous Bleeding due to Severe Skin Metastases of Breast Cancer Successfully Treated Using Mohs Paste].

We report a case of severe skin metastases of advanced right breast cancer in an 84-year-old woman. The tumor (T4bN3cM0, Stage III C)was resected in June 2011(BT+AX)after blood transfusion for severe anemia. Radiotherapy to the right chest wall and supraclavicular lymph nodes was performed, and adjuvant hormonal therapy was administered. Local recurrences in the skin of the right chest wall appeared and were resected in December 2011. Nine months later, continuous bleeding from the progressed, widespread skin metastases needed recurrent blood transfusion. After using Mohs paste twice, the bleeding stopped almost completely. Mohs paste was very useful for stopping bleeding in locally advanced, unresectable skin metastasis.

[A case of cardiac tamponade due to pericarditis carcinomatosa of breast cancer successfully treated via pericardiocentesis and systemic chemo-endocrine therapy].

We report a case of lung and bone metastases of right advanced breast cancer in a 33-year-old woman. Her breast cancer (T4bN1M1, StageIV)was resected in December 2003 (mastectomy [BT] plus axillary lymph node dissection [AX]) after local arterial infusion therapy and subsequent systemic chemo-endocrine therapy was initiated and continued. In June 2007, a computed tomography (CT) scan revealed cardiac tamponade due to pericarditis carcinomatosa. Pericardiocentesis was performed, and the bloody effusion was drained immediately. Subsequently, the sysytemic chemo-endocrine therapy was modified. In 2009, multiple cerebellar metastases were discovered and treated via whole brain irradiation. In 2010, multiple liver metastases appeared, and they were treated by intravenous (IV) administration of nab-paclitaxel. In 2011, superior vena cava syndrome appeared gradually, and it was treated via venous metallic stenting. In 2012, epidural spinal cord compression appeared gradually, and it was treated via irradiation. In November 2012, the patient died because of lymphangitis carcinomatosa; her prognosis was good, as it was approximately 5 years after the pericardiocentesis.

[A case report of liver metastasis of breast cancer successfully treated by hepatic arterial infusion of docetaxel and systemic administration of nab-paclitaxel].

We report the case of an effectively treated 50-year-old woman with liver metastasis of left breast cancer. Her breast cancer (T2N0M0, Stage IIA) was resected in November 1998 (radical mastectomy+axillary lymph nodes dissection). After this operation, tamoxifen(TAM 20 mg daily) was administered. In February 2002, a solitary liver metastasis(S5, 4 cm in diameter) was found by computed tomography(CT) scan. Hepatic arterial infusion of docetaxel(DOC 20 mg weekly)was started. In March 2003, the solitary liver metastasis had become smaller and showed partial remission (PR), but DOC intravenous injection(iv) therapy(40 mg weekly) was started because lung metastases appeared. Therefore, epirubicin+ cyclophosphamide therapy, DOC ia therapy (120 mg triweekly), and anastrozole (1 mg daily) were continued. However, in March 2005, she refused chemotherapy. In January 2011, a CT scan showed progressive disease of multiple liver and lung metastases. Nab-paclitaxel(PTX) iv therapy(400 mg triweekly) and exemestane(25 mg daily) were administered. In March 2012, a CT scan showed PR of the metastatic breast cancer. She has continued to receive nab-PTX iv therapy as an outpatient.

[Loco-regional chemotherapy at the outpatient clinic for gastric cancer patients with home enteral nutrition].

In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.

[Two case reports of metastatic liver carcinoma with the effective treatment of radiofrequency ablation and intraarterial chemotherapy].

We report two cases of metastatic liver carcinoma with the treatment of radiofrequency ablation (RFA) and intraarterial chemotherapy. The 57-year-old man of Case 1 had resectable multiple liver metastases of rectal carcinoma in November 2007. He refused a liver resection, but accepted a low anterior resection of the rectum and RFA and intraarterial chemotherapy (5-FU 1,000 mg WHD). After this treatment, he had accepted systemic chemotherapy and found no liver recurrence within a year. The 66-year-old man of Case 2 had unresectable multiple liver metastases of locally-advanced esophageal carcinoma in July 2006. He had accepted radiochemotherapy (FP+65 Gy), and then RFA and intraarterial chemotherapy (5-FU 1,000 mg WHD). After this treatment, solitary brain metastasis and lymph node metastasis of mediastinum were found and treated, and now he has been alive with systemic chemotherapy.

[A case report of intra-operative radiotherapy and gemcitabine for unresectable pancreatic body cancer].

We report an effective case of fifty-seven year-old female with unresectable pancreatic cancer. Its chief complaint of the case was epigastralgia in April 2007, and the diagnosis was locally-advanced cancer of pancreatic body (4 cm, Stage IVa) in June 2007. Laparotomy was performed, but the locally-advanced cancer was unresectable because of the invasion to the celiac trunk and superior mesenteric artery. Tumor biopsy and intra-operative radiotherapy (IORT, 12 MeV, 20 Gy) were only performed. The result of biopsy was moderately-differentiated adenocarcinoma. After laparoptomy, systemic chemotherapy (gemcitabine 1,000 mg/body) was performed once a week. After 4-set chemotherapy, her cancer pain was completely relieved and the tumor size was decreased to 25 mm on CT scan in October 2007. She has been treated as an outpatient.

Sensitization to enhanced green fluorescence protein minor histocompatibility antigen by gene transduction into dendritic cells and peritoneal exudate macrophages.

Enhanced green fluorescence protein (EGFP) has been widely applied to gene transduction in cellular and molecular biology as a reporter element. When applied to cell transplantation, it raises fundamental issues concerning cell-associated antigens, in particular, a model of minor histocompatibility antigen(s). Although it is well known that immunological behavior of minor histocompatibility antigens mimic tumor associated antigens (TAA), identified genes coding minor histocompatibility antigens are few and far between. Inasmuch as immunity and tolerance to TAA are provided by immunological behavior of minor histocompatibility antigen such as histocompatibility antigen of the Y chromosome, H-Y, it occurs to us that transgenic as well as transduced EGFP provides a useful model system to be applied to tumor immunology. In this respect, genetic modification of specialized antigen-presenting cells (APC), i.e., dendritic cells (DC), such as gene transduction of EGFP into DC, would provide one of the most important strategies in transplantation as well as tumor immunology inasmuch as DC play a key role in initiating primary immune responses, As far as gene transduction into DC is concerned, others have reported that successful gene transduction occurs in DC by adenoviral vector systems. However, our previous studies concerning EGFP transduction into DC suggested that this view should be carefully examined and interpreted. Employing adenoviral and lentiviral vector systems as well as specialized APC of rat DC and peritoneal exudate macrophages (PEM), EGFP-transduced APC were examined to determine whether and to what extent the EGFP-transduced APC were able to sensitize non-transgenic littermates against transgenic EGFP as antigen(s). Thus EGFP-transgenic cardiac isografts were transplanted to non-transgenic littermates and examined to determine if sensitization of non-transgenic littermate recipients with the EGFP-transduced APC was able to reject the test grafts in an accelerated manner. In this study, we examined this and provide further evidence that widely used viral vector systems are unable to transfer the reporter gene EGFP into mature rat DC generated from bone marrow cells (BMC), driven by Flt3/Flk2 ligand and IL-6. Nevertheless, successful gene transduction was obtained by either applying a lentiviral vector system to the developing DC progenitor cells during a long-term culture of rat BMC or by applying an adenoviral vector system to PEM. Thus, successful gene transduction into specialized APC was verified by in vivo priming of non-transgenic littermates with the EGFP-transduced APC, followed by accelerated rejection of EGFP-transgenic cardiac isografts.

[A case report of intraabdominal bleeding in unresectable pancreatic cancer after intraoperative radiotherapy].

We report a death case of 56-year-old male with unresectable pancreatic cancer. Its diagnosis was locally-advanced cancer of pancreatic head (Stage IVa) in February 2006. However, he desired no medical treatment until obstructive jaundice (T-Bil 25 mg/dL) appeared. In September 2006, endoscopic biliary metallic stenting was performed and the obstructive jaundice had improved. In November 2006, systemic chemotherapy (S-1 +gemcitabine) was performed. After the chemotherapy, vomiting had appeared because of duodenal stenosis. In December 2006, gastrojejunostomy and intraoperative radiotherapy (IORT) were performed, and the dose of oxicodon was decreased. However, in January 2007, he was suddenly in a state of bleeding-shock and died because of intraabdominal bleeding. The autopsy demonstrated the rupture of splenic pseuoaneurysm due to necrotizing pancreatitis of pancreatic tail, and cancer of pancreatic head was almost viable and IORT was not effective.

Phenotype and function of GM-CSF independent dendritic cells generated by long-term propagation of rat bone marrow cells.

GM-CSF is believed to be an essential factor for growth and differentiation of myeloid dendritic cells (DC). Employing a low-density fraction of rat bone marrow cells, we attempted to generate DC with human Flt-3/Flk-2 and IL-6. In this culture system, typical DC gradually appeared without exogenous GM-CSF supplement. Phenotypes and functions of the DC were examined. Evidence provided that the most efficient long-term outgrowth of DC progenitors was obtained by GM-CSF independent culture systems with the aid of Flt3/Flk-2 and IL-6, not with c-kit ligand and IL-6. Furthermore, CD103 (OX-62), which is widely used for rat DC separation, was found to be insufficient for enriching DC, due to the down-regulation of the marker. However, the most efficient selection of rat DC was made by CD161a (NKR-P1A), a C-type lectin family. The GM-CSF independent DC was functionally active in vitro as well as in vivo assays.