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 Sarcoid‒Like Reaction with Multiple Lymphadenopathy by Rectal Cancer after an Operation].

We are reporting on a case of lymphadenopathy after surgery for rectal cancer. The case was a 66‒year‒old female. Laparoscopic high anterior resection(D3 dissection)was performed for rectal cancer(pT1bpN0M0, pStage Ⅰ)in April 2018, and she was followed up with on an outpatient basis. In July of the same year, a painless mass had formed in the right groin. An abdominal contrast‒enhanced CT showed lymph node swelling around the right groin and external iliac artery, but the tumor markers, CEA 2.3 ng/mL and CA19‒9 <2 U/mL, were within the standard values. An inguinal lymph node biopsy was performed during the same month. Pathological examination revealed no cancer cells and formation of epithelioid granuloma with giant cells. There was no suspicion of systemic sarcoidosis based on the test results and clinical findings. From the above, the patient was diagnosed with sarcoid reaction due to the tumor. Abdominal contrast‒enhanced CT scan 2 months after the biopsy showed lymph node shrinkage and there was no recurrence 2 years after the biopsy.

Postoperative Adjuvant Chemotherapy Regimen of CAPOX Combined With Ninjin'yoeito in an Elderly Patient With Stage III Colon Cancer: A Case Report.

We report the successful management of stage III colon cancer in an elderly patient who received an adjuvant chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) with the Japanese kampo medicine ninjin'yoeito (NYT). A 75-year-old woman with a medical history of hypertension presented at another institution with fecal occult blood, and a colonoscopy that showed a type II tumor in the sigmoid colon. She was referred to our hospital for tumor resection, where colonoscopy confirmed the location of the type II tumor in the sigmoid colon. Histopathology of the biopsy specimen indicated a moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen indicated thickening of the sigmoid colon wall. Regional lymph node metastasis was suspected, but distant metastasis was not indicated. A blood examination revealed an elevated carcinoembryonic antigen (CEA) concentration (32.7 ng/ml). Following a diagnosis of cancer of the sigmoid colon, clinical stage IIIb [cT4a, N1b, M0], a laparoscopic sigmoid colectomy was performed without complications. The postoperative histopathological examination revealed a moderately differentiated to mucinous adenocarcinoma. Three of 16 retrieved lymph nodes contained malignant cells. The final tumor classification was Stage IIIb [pT4a, pN1b, M0]. The patient recovered uneventfully, and was discharged 10 days after surgery with a recommendation for adjuvant chemotherapy with CAPOX starting 4 weeks after surgery. The patient also received 7.5 g of NYT daily throughout the adjuvant chemotherapy course. She did not report any loss of appetite, general fatigue, peripheral neuropathy, neutropenia, or febrile neutropenia. During a 1-year postoperative follow-up, she has not experienced any recurrence. We conclude that NYT might be useful for reducing the adverse effects of anticancer therapy, particularly in elderly patients.

[A Case of Intra-Abdominal Desmoid Tumors Occuring Four Years after Open Radical Prostatectomy].

Desmoid tumor is one kind of fibromatosis, and much occurs the abdominal wall and outside the abdominal wall. Intra- abdominal desmoid tumor is rare at about 8%. We experienced a case of intra-abdominal desmoid tumors occurring 4 years after open radical prostatectomy with some literature review. A 72-year-old man had undergone open radical prostatectomy for prostate cancer. Four years after that resection, multiple intra-abdominal tumors measuring 56 mm in maximum diameter was identified on follow-up computed tomography, and he was referred to our department for management. We performed laparotomy and investigation of the biopsy. Immunohistochemistry of the resected specimen indicated the tumor cells were positive for vimentin and ß-catenin, and the diagnosis was desmoid. We performed partial resection of the small intestine and ileocecal resection. His postoperative course was uneventful and he was discharged on the 12th postoperative day. He has shown no sign of recurrence in the 4 months follow-up since surgery. In the past, an operation was the best treatment for intra-abdominal desmoid tumor. But it is reported that watchful waiting is also possible by the case which has no symptom and dysfunction in NCCN guidelines 2019. Further research is needed.

[Hyperammonemia with Disturbance of Consciousness during 5-FU plus Nedaplatin Therapy for Esophageal Cancer-A Case Report].

Hyperammonemia is a rare adverse event of 5-FU. Here, we report a case of hyperammonemia with disturbance of consciousness during 5-FU plus nedaplatin therapy for esophageal cancer and present a literature review. A 69-year-old man was diagnosed with cT2N2M0, cStage Ⅲ esophageal cancer. He was administered with DCF therapy as the first-line neoadjuvant chemotherapy. After the first course, he showed renal dysfunction. Therefore, as the second-line neoadjuvant chemotherapy, he was administered with 5-FU plus nedaplatin. He vomited on treatment day 5 and suddenly presented with disturbance of consciousness on treatment day 6. Blood tests showed hyperammonemia(114 µg/dL). He was treated with rehydration and branched-chain amino acid solutions, resulting in a gradual improvement of symptoms. Hyperammonemia has been reported in patients with colorectal cancer but rarely in patients with esophageal cancer. A case of hyperammonemia during the 5-FU plus nedaplatin therapy has never been reported in Japan. We should be aware that 5-FU may cause hyperammonemia and resultant disturbance of consciousness during chemotherapy with 5-FU.

[A Case of Obstructing Rectal Cancer with Obstructive Colitis Resected after Neoadjuvant Chemotherapy to Avoid Anastomotic Leakage].

A 61-year-old male was referred to our department after decompression of the transanal ileus tube due to a rectal cancer obstruction. Colonoscopy revealed a circumferential type 2 tumor, 4 cm from the anal verge. The tumor was diagnosed as rectal cancer tub1-2, Group 5 on biopsy analysis. Longitudinal ulcers descending to the sigmoid colon were present and obstructive colitis was suspected. Enhanced computed tomography showed wall thickness in the Ra, Rb rectum and swelling of the mesorectum lymph node, but distant metastases were not identified. We diagnosed the patient with Ra, Rb rectal cancer cT4aN1aM0, cStage Ⅲb. Because of the risk of anastomotic leakage with obstructive colitis, we planned neoadjuvant chemotherapy(SOX therapy)after laparoscopic transverse colostomy. After neoadjuvant chemotherapy, colonoscopy revealed improvements in the obstructive colitis. The tumor was reduced in size and the chemotherapy appeared effective. We performed laparoscopic rectal super low anterior resection with resection of the D3 lymph node. Histopathological examination revealed tub1, ypT3, ypN0, and the chemotherapeutic outcome was rated as Grade 1a. The final diagnosis was Ra, Rb rectal cancer with ypT3ypN0M0, ypStage Ⅱa.

Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial.

AIM: This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer. PATIENTS AND METHODS: Each patient received four cycles of 260 mg/m2 nab-paclitaxel with 6 mg/kg trastuzumab (8 mg/kg as the loading dose) every 3 weeks (q3w) followed by four cycles of FEC (500/100/500 mg/m2) q3w. The primary endpoint was pathological complete response (pCR) rate. RESULTS: Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%. CONCLUSION: Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

[A Case of Metachronous Metastasis to the Pancreas from Ascending Colon Cancer after Subtotal Stomach-Preserving Pancreaticoduodenectomy(SSPPD)].

A67 -year-old man was diagnosed with ascending colon cancer and multiple liver metastases and underwent laparoscopic right hemicolectomy(D3 lymphadenectomy). Pathological examination indicated tubular adenocarcinoma(tub1, pT4apN2H2M1[HEP], pStage Ⅳ). After chemotherapy, he underwent hepatectomy. One year and 9 months after the first operation, obstructive jaundice appeared. Abdominal computed tomography revealed a tumor 2 cm in size in the head of the pancreas. After several detailed examinations, he was diagnosed with pancreatic metastasis of ascending colon cancer. After partial resection of the left lung metastasis, pancreaticoduodenectomy(SSPPD-Ⅱ A-1, D1 lymphadenectomy)and low anterior resection(LAR)for early rectal cancer were performed. The tumor was positive for CDX2(+), resulting in a diagnosis of pancreatic metastasis. There has been no indication of recurrence 8 months after the pancreatic surgery. Resectable pancreatic metastasis from colon cancer is rare, and there are no clear indications for resection. Some cases of long-term survival have been reported; however, further studies are needed in order to establish a consensus.

[A Case in Which pCR Was Obtained by S-1 plus Oxaliplatin Therapy Administered as Neoadjuvant Chemotherapy for Advanced Gastric Cancer].

A 78-year-old man presented with anemia, with a hemoglobin level of 6.7 g/dL, during follow-up for angina pectoris and paroxysmal atrial fibrillation. Upper gastrointestinal endoscopy revealed type 2 advanced gastric cancer(por), and abdominal computed tomography(CT)showed multiple lymph node metastases. He was diagnosed with advanced gastric cancer, cStage Ⅲ(cT3N1M0). He received neoadjuvant chemotherapy in 3 courses of SOX(80mg/m / 2/day of S-1 on days 1-14 and 7 days of rest, and 100mg/m2 of oxaliplatin on day 1). Grade 1 thrombocytopenia was observed, but it resolved without any other major side effects. Upper gastrointestinal endoscopy revealed a marked reduction in the primary lesion, and abdominal CT showed a significant reduction in the metastatic lymph node. We performed laparoscopic distal gastrectomy(D2+No. 14v)for advanced gastric cancer ycT1N(+)M0, ycStage ⅡA. Histological assessment revealed no evidence of residual tumor cells in the primary tumor or lymph nodes, and the histologic response was classified as Grade 3, pathological complete response(pCR). We report a case in which pCR was obtained by SOX therapy administered as neoadjuvant chemotherapy for advanced gastric cancer.

[A Case of Sister Mary Joseph's Nodule from Transverse Colon Cancer Effectively Treated with SOX plus Bevacizumab Chemotherapy].

A 47-year-old woman presented with a hard umbilical nodule that appeared red and was painful. A biopsy of the umbilical nodule revealed adenocarcinoma. As a result of general examinations, the patient was diagnosed with umbilical, hepatic, and ovarian metastases from transverse colon cancer. She was treated with S-1 and oxaliplatin(SOX)plus bevacizumab chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and umbilical and hepatic metastases had reduced in size. We considered this to be a partial response and thus administered 4 additional courses of SOX plus bevacizumab chemotherapy. Finally, she remained well for 22 months and achieved relatively good prognosis. An umbilical metastasis from an internal malignancy is known as a Sister Mary Joseph's nodule, and it has very poor prognosis. Most studies show that the survival period from the time of diagnosis is within 1 year. However, our case suggests that novel anti-cancer drugs or molecular-targeted agents may improve survival.

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.

[A Case of Apocrine Carcinoma of the Breast].

A 76-year-old postmenopausal woman presented with a bloody attachment on the left nipple. She had a 3 cm-sized tumor in her left breast. Mammography showed a spiculated irregular mass. Ultrasonography showed a 38 mm, low echoic mass with an irregular border. Core needle biopsy examination indicated apocrine carcinoma of the breast, ER(-), PgR(-), and HER2(-). An overall examination showed no distant metastasis. We diagnosed her with apocrine carcinoma of the breast(T2N0M0, cStageⅡA). We performed total mastectomy with sentinel lymph node biopsy. The postoperative histopathological examination revealed apocrine carcinoma without lymph node metastasis. The patient recovered uneventfully and was discharged 8 days after the surgery. She has not experienced any recurrence for 1 year and 7 months after the surgery.

[Transanal Minimally Invasive Surgery for Rectal Neuroendocrine Tumor].

A 57-year-old woman was admitted to our hospital due to a suspected rectal tumor at previous doctor. Colonoscopy showed a submucosal tumor with 8mm yellowish protrusions and smooth surfaces in the rectum, 5 cm from the anal verge. Endoscopic ultrasonography showed the appearance of the internal portions of the tumor to be relatively uniform in low echoic imagery. The tumor was located in the second to third layer. Histopathological findings showed neuroendocrine tumor- G1. We performed transanal minimally invasive surgery with GelPOINT®Path. Under general anesthesia, complete fullthickness excision of the rectal lesion was performed. Primary closure was accomplished using a 3-0 braided absorbable suture. The operation duration was 24 min; blood loss was very little in this case. The patient recovered uneventfully and was discharged 2 days after the operation. There was no anorectal dysfunction and no local and distant recurrence during the postoperative follow-up of 1 year 3 months. Transanal minimally invasive surgery with GelPOINT®Path was an effective treatment for the safe removal of small rectal tumor indicated for local resection.

[A Case of Emergency Surgery for Intussusception Due to Cecal Cancer].

A 79-year-old woman was admitted to the hospital because of continuous right lower abdominal pain lasting for 1 day. There was tenderness with signs of peritoneal irritation at the right lower abdomen along with a palpable mass. With the diagnosis of intussusception of the ileocecal region by CT examination, an emergency surgery was performed under general anesthesia. By laparoscopic ileocecal resection with lymph node dissection, the ileocecal region was found invaginated into the transverse colon, although this was easily reduced by Hutchinson's procedure. The histological diagnosis of the tumor was highly differentiated adenocarcinoma in Stage Ⅲb. The postoperative course was uneventful and the patient remained in good health without any recurrence during a follow-up period of 12 months. When a patient has a sign of peritoneal irritation, such as in our case, and intestinal tract necrosis and perforation by intussusception cannot be excluded, it is necessary to perform an emergency surgery.

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.

[Pneumatosis Cystoides Intestinalis after Hematopoietic Stem Cell Transplantation for Malignant Lymphoma - A Case Report].

A 47-year-old man underwent hematopoietic stem cell transplantation for malignant lymphoma. He developed acute skin graft versus host disease(GVHD)and pneumomycosis which were treated with steroids. One hundred and fifteen days later, the patient had a diagnosis of free gas images in the abdominal cavity and streakly air collections in the bowel wall from the ascending colon to the sigmoid colon in the CT scan. He was asymptomatic and his physical examination was unrevealing. We diagnosed his condition as pneumatosis cystoides intestinalis(PCI). He was managed conservatively with the high concentration oxygen administration. The CT scan performed 3 days later revealed the marked improvement of intramural gas and disappearance of free gas. We considered image in the abdominal cavity that the occurrence of PCI was related to the damage of the bowel mucosa due to long term corticosteroid administration. In patients demonstrating PCI with free air in the abdominal cavity, it is important to evaluate not only the diagnostic date based on the physical, laboratory, and imaging findings, but also their medical history. Furthermore, it is important to make a correct diagnosis to avoid unnecessary surgery.

[A Case of Recurrent Stenosis after Metallic Stenting for Esophagogastric Junction Adenocarcinoma with Peritoneal Metastases].

A 65-year-old man presented with severe strictures from the esophagogastric junction to the body of the stomach and was histopathologically diagnosed with adenocarcinoma. Computed tomography showed multiple peritoneal metastases. A long, covered metallic stent was placed, and chemotherapy was started. Subsequent granulation from the oral side of the stent caused stricture formation, and a covered stent was also placed. After 8 months, granulation from the oral side of the stent caused recurrent stricture formation. We again placed a metallic stent. Successful chemotherapy for stomach cancer with long-term benefit is possible with new molecularly targeted drugs. Stenting may cause adverse events such as stenosis, but can enable oral intake and is minimally invasive. This report describes a case that required multiple stent placement and reviews the relevant literature.

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.

[Multidisciplinary Therapy for Advanced Gastric Cancer with Liver and Brain Metastases].

A 68-year-old man was admitted to our hospital. He was diagnosed with advanced gastric cancer with multiple liver metastases. The primary tumor was treated with distal gastrectomy with D2 dissection and anti-cancer agents, and then he was scheduled for a 2-stage hepatic resection. After surgery, the liver metastases disappeared, and he was diagnosed with a CR. However he complained of dizziness and was diagnosed with metachronous brain matastasis. Multidisciplinary treatment including resection and radiotherapy was administerd and he survived for 5 years after diagnosis.

[A Case of Laparoscopic Gastrectomy in a Patient with Refractory Vasospastic Angina].

We report a case of laparoscopic gastrectomy in a patient with refractory vasospastic angina. An 83-year-old man received 2 types of oral coronary vasodilators but complained of chest pain about twice a week thereafter. He was diagnosed with refractory vasospastic angina. Upper gastrointestinal endoscopy was performed for tarry stools and revealed a type 2 tumor in the anglar posterior wall. CT revealed no lymph node swelling or metastasis. Laparoscopic gastrectomy was performed, and intravenous administration of coronary vasodilators was started before the operation. During the operation, coronary spasm could be prevented while being careful not to induce circulation change, bleeding, or traction of the peritoneum. Many cases of coronary spasm-related angina in the absence of a history of angina have been reported during non-cardiac operations. In such cases, careful coronary spasm is necessary.