An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer.

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

[A Case of Sigmoid Colon Cancer It Was Found from Penetration of Sigmoid Diverticulum].

A 52-year-old woman presented with sudden left lower abdominal pain, fever, and vomiting. As the symptom got improved immediately she went home then. She consulted our hospital with chief complaint of the left lower abdominal mass. Abdominal computed tomography revealed sigmoid colon cancer with abscess. She was diagnosed with sigmoid colon cancer via colonoscopy. Sigmoidectomy including partial resection of the abdominal wall was performed(D3 lymphadenectomy). Surgical specimen showed penetration of diverticulum on mucous membrane of the lesion which had been thought of a abdominal wall permeation and a tumor of I sp type at anal side. Pathological examination showed diverticulitis with penetration and the tumor was tubular adenocarcinoma(tub1, pT1bpN0, pStage I ). We had doubted penetration of sigmoid colon cancer most, but the cause of penetration turned out to be diverticulitis. We experienced a case in which we could performed surgery of sigmoid colon cancer and penetration of diverticulum at the same time.

Safety and Efficacy of Low-dose Nanoparticle Albumin-bound Paclitaxel for HER2-negative Metastatic Breast Cancer.

BACKGROUND/AIM: Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m2/3weeks regimen. PATIENTS AND METHODS: Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. RESULTS: Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. CONCLUSION: Nab-PTX 175 mg/m2/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer.

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

[A Case of Huge Advanced Neuroendocrine Carcinoma of the Transverse Colon Resected Successfully].

The patient, 49-year-old woman, who was referred to our hospital in August 2016 because of left abdominal pain. The abdominal CT scan showed a large tumor, over 10 cm dimeter at splenic flexure of the transverse colon, and colonoscopy detected transvers colon cancer(por, cT4b, cN1, M0, cStage III A). There was no distant metastasis, although invasion to the retroperitoneum and the abdominal wall. Left hemicolectomy was successfully performed with D3 lymph node dissection. Pathological diagnosis was endocrine cell carcinoma, pT4a(SE), pN0, M0, pStage II . The Surgical margin was completely free of carcinoma(R0). The postoperative course was uneventful, and she has been in good health with no recurrence for 8 months after surgery. Neuroendocrine cell carcinoma is recommended for adjuvant treatment based on small cell lung cancer, but there are not effective clinical trials nor established treatment methods because it is rare disease.

[A Case of Curatively Resected Ascending Colon Cancer after Long-Term Chemotherapy Found in Abdominal Trauma].

A 46-year old man presented with lower right quadrant abdominal pain caused by abdominal trauma. Abscess drainage was performed after the diagnosis of retroperitoneal abscess in the ileocecal portion of the colon. Type 2 advanced cancer was found in the cecum and ascending colon. Surgery was performed after improvement of inflammation. Considering the difficulty of curative resection for retroperitoneal invasion, we first performed ileo-transverse colon anastomosis. After surgery, the patient received FOLFOX with panitumumab(Pmab)as neoadjuvant chemotherapy. After 6 courses of this regimen, contrast enhanced computed tomography revealed shrinkage of the tumor. We performed a second surgery but the tumor was unresectable because of retroperitoneal invasion. After 47 courses of chemotherapy(5-FU plus LV with Pmab), the tumor was stable and we observed no distant metastasis. A third surgery was performed, and we were able to perform ileocecal resection including the retroperitoneum. The pathological diagnosis was pT4b(SI), pN1, ly2, V2, pPM0, pDM0, R0, pStage III a. On histological examination, the efficacy of chemotherapy was evaluated as Grade 1a. The patient received adjuvant chemotherapy with capecitabine and remains healthy without any evidence of recurrence more than 10 months after surgery.

[A Case of Early Colon Cancer Discovered by Granulomatous Inflammation of the Ileum Caused by Fish Bone].

A 63-year-old man presented with abdominal pain in the lower right quadrant and high fever. An abdominal CT scan on admission revealed ileocecal wall thickening and inflammation of the terminal ileum. No foreign body was observed on CT scan. He received antibiotic therapy, but no improvement was noticed. Colonoscopy showed a sporadic type 0- I s+ II c lesion in the sigmoid colon. Histological examination showed well differentiated adenocarcinoma. We diagnosed the patient as having inflammation of the terminal ileum and sigmoid colon cancer. Laparoscopic surgery was performed. Inflammation was present in the terminal ileum, and local resection and sigmoidectomy were performed. A foreign body that appeared to be a fish bone was present in the resected specimen, and this led to the diagnosis of granulomatous inflammation of the ileum caused by fish bone. In the sigmoid colon, the pathological diagnosis was pT1b(sm), pN0, ly1, v1, pDM0, pPM0, R0, pStage I . He was discharged without any complication and has not shown any evidence of recurrence more than 1 year after surgery.

A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

[Consideration of Safety of Implant-Based Breast Reconstruction with Postreconstruction Radiotherapy for Breast Cancer].

There is controversy as to whether immediate autologous breast reconstruction followed by postoperative radiotherapy has acceptable complications and aesthetic outcomes. PURPOSE: To evaluate the interval between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy and immediate expander-implant reconstruction, and to evaluate locoregional and distant control and cosmesis in these patients. METHODS AND MATERIALS: Between 2011 and 2015, 9 patients with breast cancer were treated at our institution with definitive mastectomy and axillary lymph node dissection followed by immediate tissue expander placement and postreconstruction radiotherapy. We reviewed the complications of implant-based breast reconstruction followed by postreconstruction radiotherapy. RESULTS: The timing of irradiation was after implant insertion for 8 patients and after tissue expander insertion for 1 patient. The mean follow-up was 601 days. There were no unacceptable complications or local recurrences. CONCLUSIONS: For the majority of patients, overall symmetry, aesthetic results, and patient satisfaction were high. Breast reconstruction using tissue expansion and implants is an acceptable option for the subset of patients who may undergo postreconstruction radiotherapy.

[Examination of Distal Gastrectomy in Our Hospital - Comparison of the Contents of Lymphadenectomy].

It has now been more than 20 years since laparoscopic gastrectomy was introduced in Japan, and the 2014 guidelines recommend laparoscopic distal gastrectomy as a treatment for cStage I gastric cancers. This operation facilitates minute lymphadenectomy via the option of enlarging the image, but there are some difficulties associated with limited range of motion. A hallmark of gastrectomy for gastric cancer is the widespread dissection of lymph nodes, and the limits imposed by laparoscopic forceps can complicate the operation. In this study, we subdivided regional lymph nodes, examined distal gastrectomy cases in our hospital, and compared the contents of lymphadenectomy.

[Two Cases of Metastatic Rectal Cancer Patients Who Received Chemotherapy with FOLFOXIRI plus Bevacizumab].

We report 2 cases of metastatic rectal cancer patients who received chemotherapy with FOLFOXIRI plus bevacizumab(Bev). Case 1: A 54-year-old woman diagnosed with advanced rectal cancer with synchronous liver metastasis underwent a laparoscopic low anterior resection. After the operation, she received FOLFOXIRI plus Bev treatment, and experienced Grade 4 adverse events, including dyspnea and ventricular fibrillation(Vf). After chemotherapy, no other metastasis was detected except a liver metastasis, and partial resection of the liver was performed. Histopathological evaluation revealed that the effect of the chemotherapy was Grade 1a. After liver resection, FOLFOXIRI plus Bev was administered, and a recurrence of the rectal cancer was not detected. Case 2: A 44-year-old woman was diagnosed with advanced rectal cancer with synchronous liver metastasis, distant lymph nodes metastasis, and vaginal invasion. First a colostomy was performed and FOLFOXIRI plus Bev treatment was administered. Grade 3 adverse events, including tremor, neuralgia, and anemia occurred, and chemotherapy was stopped for 3 months. Her adverse events were not under control when progression of the disease was detected, and her treatment was changed to another chemotherapy regimen.

[An Autopsy Case of an Elderly Patient with Signet-Ring Cell Carcinoma of the Breast Derived from Lobular Carcinoma].

A 90-year-old woman was referred to our hospital because of abdominal distension and pretibial edema. No tumors were palpable in either breast. Her abdomen was distended and palpitation was noticed. Laboratory examination revealed hypercalcemia and elevated levels of tumor markers(PIVKA- II , CEA, CA19-9, SCC). Contrast-enhanced computed tomography(CT) showed pleural effusion and ascites, an approximately 17-mm high-contrast mass in the D area of the left breast, and osteolysis of the dorsal lumber spine. We initiated treatment for pleural effusion, ascites, and hypercalcemia. However, on her 11th day in the hospital, hematemesis was observed and the patient died. We suspected metastasis of a malignant tumor, but a primary lesion had not been identified; therefore, an autopsy was performed. Autopsy showed a 17-mm mass in the D area of the left breast. Histopathological examination showed the growth of a signet-ring cell tumor that was immunohistochemically ER-positive, PgR-positive, and E-cadherin-negative. The patient was diagnosed with primary signet-ring cell carcinoma of the breast derived from lobular carcinoma. We reported a rare case of primary signet-ring cell carcinoma of the breast with a review of literature.

[Ovarian Cancer Rupture Causing Acute Abdomen That Required Emergency Surgery - A Case Report].

A 50-year-old post-menopausal woman with sudden lower abdominal pain was transported to hospital by ambulance. Abdominal symptoms and computed tomography(CT)suggested a diagnosis of acute pan-peritonitis due to gastrointestinal perforation, and emergency surgery was performed. The intraoperative findings led to a diagnosis of a ruptured cyst in the left ovary, a portion of which was observed to be partially solid, and therefore, ovarian cancer was suspected. Accordingly, a unilateral(left)salpingo-oophorectomy and intraperitoneal drainage were performed with assistance from a gynecologist. Following a diagnosis of ovarian clear cell adenocarcinoma based on histopathological examination, the patient underwent further debulking surgery at a later date, followed by postoperative chemotherapy. In acute pan-peritonitis associated with a large quantity of ascites in women, the rupture of ovarian tumors should be considered as a possible etiology. The therapeutic strategy for ovarian cancer is determined according to post-operative staging, even during emergency surgery. It is therefore important not only to repair the rupture, but also, if possible, to perform a diagnosticbiopsy or resection.

[A Case of Small Intestinal Malignant Lymphoma Presenting with Perforated Peritonitis].

An 85-year-old man presented to the emergency department with vomiting. He had tenderness in the left abdomen and under the umbilicus. Laboratory data showed an increase in the inflammatory response. Enhanced abdominal computed tomography showed thickening ofthe small intestinal wall in the lower left abdomen with a small amount ofadjacent free air. The fat tissue around the small intestine also revealed a high density area suggestive of inflammation. A diagnosis of peritonitis caused by intestinal perforation was made and an emergency operation was performed. We resected part of the ileum about 90 cm from the ileum end. The resected specimen showed a 1 by 1 cm mass with an ulcer and perforation at the base of the tumor. Histopathological findings revealed densely increased numbers of monomorphic medium-sized lymphoma cells infiltrating into all layers ofthe intestine. Immunohistochemically, the lymphocytes were positive for CD3, CD20, CD30, and CD79a. We diagnosed diffuse large B-cell lymphoma. Two cycles ofchemotherapy were given post-operatively. A recurrence was not observed. After chemotherapy he was transferred to rehabilitation.

[A Case of Eosinophilic Enteritis Needed to Distinguish from a Tumor of the Small Intestine].

A 75-year-old woman was diagnosed with aplastic anemia 6 months ago and was under follow-up at our hospital. She had originallypresented to our hospital because of ongoing diarrhea and abdominal pain. Her blood tests showed a rise in inflammatorymarkers (WBC count was 6,900/mL[eosinophil was 1.3%]and CRP was 8.60mg/dL). Her abdominal computed tomography(CT)scan showed gastric wall and small intestine edema as well as ascites. There was no evidence of free air. We diagnosed her with generalized peritonitis and performed an emergencyoperation . Intra-operatively, moderate amounts of yellowish ascitic fluid were noted, as was a diffuse reddening of the small intestine. We performed a partial resection of the small intestine. Histopathological examination showed transmural infiltration of inflammatorycells mainly comprising eosinophilic leukocytes. Eosinophils were also present in the ascitic fluid. Post-operative blood tests confirmed eosinophilic, and we diagnosed her with eosinophilic enteritis. She was started on corticosteroids and her symptoms improved immediately. We report a rare case of eosinophilic enteritis with a review of the pertinent literature.

[A Case of HER2-Positive Breast Cancer Treated with Nipple-Sparing Mastectomywith Immediate Reconstruction Using a Tissue Expander after Nab-Paclitaxel Combined with Chemotherapy].

A 59-year-old woman presented to our hospital with a mass in her left breast. Mammography and ultrasound showed a 9 ×11×12mm mass in her left breast, and left axillary lymph adenopathy. Core needle biopsy and pathological examination confirmed the diagnosis of ER-negative, PgR-negative, HER2-positive invasive ductal carcinoma with axillary lymph metastasis. Dynamic computed tomography(CT)and bone scintigraphy showed no metastasis. A diagnosis ofbreast cancer with stage II A(T1N1M0)was made, and we started neoadjuvant chemotherapy. After 4 cycles of chemotherapy with 5-fluorouracil/ epirubicin/cyclophosphamide in 3-weekly cycles, we administered combination chemotherapy ofnab -paclitaxel and trastuzumab in 3-weekly cycles. After 7 months, the tumor disappeared and the axillary lymph node got significantly smaller. We performed nipple-sparing mastectomy/axillary lymph nodes dissection/tissue-expander placement. The pathological examination ofthe resected tumor confirmed a pathological complete response(pCR). The patient was treated with implant reconstruction and adjuvant therapy. One year has passed after the surgery, and no significant problem has been observed.

[Effectiveness of Intraoperative Histologic Assessment of Surgical Margins for Breast-Conserving Surgery].

BACKGROUND: The effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery is unclear. In this study, we investigated the effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery. METHODS: Sixty-six patients who underwent breast-conserving surgery for breast cancer at our hospital between January 2007 and December 2013 were retrospectively examined for an association between the surgical margin status and locoregional recurrence. The surgical margins were then evaluated by intraoperative histologic assessment. RESULTS: The median observation period was 52 months. Positive margins were found in 14 patients (21%). A total mastectomy was performed in 9 patients, and additional resection in 5 patients. In the permanent tissue sample, the intraoperative assessment was found to be false negative in 2 patients (3.8%), who received boost irradiation postoperatively. No locoregional recurrence was observed in all patients who underwent additional resection or total mastectomy due to positive margins. The rate of margin positivity was significantly higher in invasive lobular carcinomas and in cancers with intraductal extension. CONCLUSIONS: Intraoperative histologic assessment of the surgical margin was useful for reducing the rate of local recurrence.

[A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy].

We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.

Retrospective analysis of capecitabine and oxaliplatin (XELOX) plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer.

XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222-409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.

[A case of anastomotic recurrence of gastric cancer who underwent esophagojejunostomy, treated with S-1 monotherapy leading to complete response (CR)].

A 67-year-old male with an anastomotic recurrence of gastric cancer who underwent esophagojejunostomy, was treated with S-1 monotherapy leading to a complete response (CR). The patient was diagnosed with gastric cardia cancer and underwent a total gastrectomy with lymph node dissection. Two years and 2 months after surgery, the patient was administered S-1 100 mg/day (4-week administration and 2-week rest) because anastomotic recurrence was confirmed. The patient was unable to take anything by mouth, but this chemotherapy could be orally administered after one course. After six courses, tumor tissue completely disappeared and he had a CR. Administration of S-1 was continued for eight courses and then discontinued. There was no relapse for two years after discontinuation.