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We report a case of sphenoid bone metastasis from breast cancer detected with diplopia, as first site of recurrence. Forty- year-old woman with left breast cancer underwent breast-conserving surgery and sentinel lymph node biopsy. The diagnosis was papillotubular carcinoma, pT1pN0, ER(+), PgR(+), HER2(-). Tweleb years later, the examination of diplopia revealed left abducens nerve palsy for sphenoid bone metastasis from breast cancer. Radiation therapy(a total dose of 36 Gy with VMAT)was administrated as topical treatment, but diplopia did not improve. After that, systemic treatment was performed, and 2 years and 6 months have passed since the recurrence was found, she is still alive. We need to be careful of orbital metastasis as a symptom of metastasis from breast cancer.

Background Vascular endothelial growth factor (VEGF) is a key player in angiogenesis, and bevacizumab, a humanized monoclonal antibody against VEGF-A, is already utilized in daily clinical practice coupled with chemotherapy for locally advanced and metastatic breast cancers (ABC). Although the impact of bevacizumab plus paclitaxel therapy on PFS was prominent, no OS benefit has been demonstrated so far. Identification of a robust biomarker for bevacizumab therapy in terms of benefit on OS is a critical issue. Since VEGF modulates various functions of cancer immunity, direct inhibition of VEGF, in addition to vascular normalization by bevacizumab may lead to improvement of immune microenvironment, resulting in favorable prognosis in patients. On the basis of this aspect, predictive efficacy of peripheral immune related parameters were investigated in patients treated with bevacizumab plus paclitaxel. Method A total of 182 patients with locally advanced and metastatic breast cancers treated with bevacizumab plus paclitaxel were retrospectively recruited from three institutes. We measured neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in the peripheral blood taken at baseline (the same day just before start of 1st treatment). Bevacizumab 10 mg/kg on days 1 and 15 and paclitaxel 80 or 90 mg/m2 on day 1, 8, and 15 of each 28-day cycle were administered intravenously. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0mg/dL, respectively and baseline values of these factors were measured. Results We divided the patients into NLR-high (n=101) and -low (n=81); CRP-high (n=62) and -low (n=89). The progression-free survival (PFS) of patients with NLR-low was significantly longer than that of patients with NLR-high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.31-0.70; p=0.0002). In addition, OS of patients with NLR-low was significantly better than those with -high (22.2 vs. 13.5 months; HR, 0.55; 95% CI, 0.38-0.80; p=0.0017). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with -high (HR, 0.42; 95% CI, 0.27-0.66; p Citation Format: Hiromi Ozawa, Yoshimasa Miyagawa, Ayako Yanai, Takehiro Yanagawa, Jyunichi Inatome, Chiyomi Egawa, Arisa Nishimukai, Kaori Takamoto, Takashi Morimoto, Atsushi Sata, Reiko Fukui, Ayako Bun, Tomoko Higuchi, Yukie Fujimoto, Michiko Imamura, Yasuo Miyoshi. Baseline neutrophil-to-lymphocyte ratio and C-reactive protein predict efficacy of bevacizumab plus paclitaxel therapy for locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-49.

The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic breast cancers. A total of 179 patients treated with bevacizumab plus paclitaxel were recruited from three institutes in the test cohort. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0 mg/dL, respectively, and baseline values of these factors were measured. The PFS of patients with NLR-low was significantly longer than that of patients with -high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.48, 95% confidence interval (95% CI), 0.31–0.73; p = 0.0004). OS of patients with NLR-low was significantly better than those with-high (22.2 vs. 13.5 months; HR, 0.57, 95% CI, 0.39–0.83; p = 0.0032). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with patients with -high (HR, 0.44, 95% CI, 0.28–0.68; p = 0.0001 and HR, 0.39, 95% CI, 0.26–0.61, p < 0.0001, respectively). In the validation cohort from two institutes (n = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low (p = 0.0344 and p = 0.0233, respectively) and CRP-low groups (p < 0.0001 and p = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.

The patient is an 85-year-old female who had previously undergone a mastectomy for right breast cancer at the age of 42 years. In September 2020, she visited our hospital with a chief complaint of a chest wall tumor. Physical examination revealed a 3×3 cm ulcerative lesion on the right side of the center chest wall. She underwent a skin biopsy of the tumor under local anesthesia and was diagnosed with a recurrence of right breast cancer(ER positive, PR positive, HER2 negative). PET-CT revealed localized skin thickening on the right side of the sternum and FDG accumulation in the same area, with no other findings suggestive of distant metastasis. Treatment was started with anastrozole and is still ongoing. In this article, we report a very rare case of recurrence 43 years after surgery.

The patient was a 56-year-old woman. who was aware of a tumor in her left axilla and consulted a nearby doctor. She was referred to our hospital for a detailed examination. No abnormalities were found in the breast by visual inspection, mammography, or breast ultrasound examination. One 29 mm swollen lymph node was found in the axilla. Fine needle aspiration cytology revealed malignant lymphoma; thus, so axillary lymph node excision biopsy was performed, and a diagnosis of axillary lymph node metastasis of breast cancer was made. However, no abnormalities were found. Based on the information presented above, the patient was diagnosed with occult breast cancer cT0N1M0, Stage ⅡA, and breast preservation plus axillary lymph node dissection up to level Ⅱ was performed. No metastases were found in the dissected lymph nodes. The treatment policy for occult breast cancer has not yet been established. We report this case with a review of the literature.

Five patients with gastric metastasis from breast cancer were treated in our hospital. About the histopathological types of primary breast cancer, 4 patients were invasive ductal carcinomas and 1 was invasive lobular carcinoma. One patient was found by gastrointestinal fiberscopy for a detailed examination of her high CEA, 2 for stenosis, 1 for bleeding and 1 for epigastralgia. After the diagnosis of gastric metastasis, 2 patients were treated with chemotherapies, 1 with hormone therapy and 2 with palliative treatments. One of them was treated with gastroduodenal stenting for pyloric stenosis, but she was died by bleeding from gastric lesion. Based on the results, constriction and bleeding with gastric metastasis is considered to be severe condition in the treatment of metastatic breast cancer.

The patient was a 77-year-old woman. She underwent a partial gastrectomy at the age of 40, and a partial colectomy at the age of 75 following a diagnosis of a carcinoid. In November 2019, a 1.5 cm mass with a clear boundary was found in the pancreatic tail, which was strongly stained uniformly. And furthermore, multiple masses between 2 cm and 3 cm with a clear boundary was found inside liver segment S1 and S6 and S7 and S8 on CT, which was strongly stained at the edge in the early phase and was seen as a low density area in the late phase. At a result of image examination, it was diagnosed as a pancreatic tail neuroendocrine tumor and its multiple liver metastases. The distal pancreatectomy, posterior segmentectomy, and partial S1 lt and S8 liver resection were performed. With postoperative pathological diagnosis, the pancreatic tumor was accessory spleen, and liver tumor were epithelioid type GIST which were positive for CD34 and PDGFRA and negative for c- kit. The pathology specimen of colectomy was re-examined, and the diagnosis from the previous surgery was changed to GIST from a carcinoid. Epithelioid type GIST was associated with a PDGFRA gene mutation and was known to have many gastric origins. Based on the clinical course, it was diagnosed as recurrence of gastric GIST at 40 years after 30 years or more.

A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.

We report a case of liver metastases of ampullary carcinoma that achieved clinical complete response after gemcitabine plus cisplatin(GC)combination chemotherapy. A 69-year-old man with obstructive jaundice was diagnosed with ampullary carcinoma and underwent laparoscopic pancreaticoduodenectomy. Postoperative histopathological examination revealed pT3aN0M0, Stage ⅡA adenocarcinoma of the papilla of Vater. Five months after surgery, multiple liver metastases were identified by CT and MRI. The patient received GC chemotherapy intravenously at doses of 1,000 and 25mg/m2 on days 1 and 8, respectively, every 3 weeks. After 3 courses of GC chemotherapy, a CT scan revealed that the liver metastases reduced in size, and PR was achieved based on the RECIST standard. However, Grade 3 neutropenia appeared. After 7 courses, the liver metastases disappeared, and the patient had achieved CR. After 9 courses, the clinical CR continued. Approximately 14 months have passed since the recurrence, and the patient is currently alive.

A therapeutic guideline for sigmoid volvulus (SV) has not been established, and the most recommended surgical procedure for SV has not been determined. Our objective is to assess the usability of elective laparoscopic sigmoidectomy and the feasibility of single-incision laparoscopic surgery for SV following endoscopic reduction. SV typically affects the elderly and accounts for 1% to 7% of intestinal obstructions in Western countries. We report on 3 patients with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction, and we first describe single-port surgery for SV. We discuss the 3 patients (a 79-year-old male, an 88-year-old female, and a 67-year-old female) with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction. All 3 patients underwent laparoscopic sigmoidectomy, and 2 patients underwent single-port laparoscopic surgery without complications. Recurrence of volvulus was not seen during the course of 12 to 24 months. In experienced hands, elective laparoscopic sigmoidectomy after colonoscopic detorsion is a valuable alternative, and single-port surgery is also feasible.

Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations.Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients. Functional analyses were then performed for the novel mutations we detected.We identified no mutations in primary tumors and six mutations in five recurrent tumors, including three types of known mutations (Y537C, Y537N, and D538G) and two novel mutations (E279V and G557R). We also identified seven mutations in five plasma samples, including three types of known mutations (S463P, Y537S, and D538G) and one mutation not reported in COSMIC database (L536H). All nine patients with ESR1 mutations were treated with aromatase inhibitors (AIs) prior to sampling, and the mutations were frequently detected in patients who received AI treatments in the metastatic setting. Among the three novel mutations (E279V, L536H, and G557R), L536H, but not E279V and G557R, showed ligand-independent activity. All three mutant proteins showed nuclear localization and had no relation with non-genomic ER pathways.Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

A 64-year-old man presented with a chief complaint of abdominal pain. An abdominal computed tomography (CT) scan showed a mass 30-mm in diameter at the splenic flexure, and we diagnosed a retroperitoneal abscess. Conservative therapy was successful, and the patient was discharged. However, 1 month later, he again experienced abdominal pain. To reassess the abscess, contrast-enhanced abdominal CT was performed. In addition to the retroperitoneal abscess, the CT scan showed an approximate 30-mm mass in the head of the pancreas with no contrast uptake. The abscess was also detected by endoscopic retrograde pancreatography. We suspected but could not confirm pancreatic cancer. Two months later, the patient developed obstructive jaundice. At this time, we diagnosed pancreatic cancer, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The histopathologic diagnosis was pancreatic cancer, T4, N0, M0, Stage IVa. The postoperative course was favorable, and the patient received postoperative adjuvant chemotherapy. He remains alive without recurrence 15 months after surgery.

A 66-year-old woman was diagnosed with pancreatic tail cancer, and she was referred to our hospital. Abdominal computed tomography(CT)revealed a tumor(2.5 cm in diameter)in the pancreatic tail, with invasion to the spleen and splenic vein. In February 2013, we performed distal pancreatectomy with splenectomy, left adrenal gland resection, and D2 lymph node dissection. Diagnostic peritoneal lavage cytology during surgery was positive; however, we performed curative resection because there were no signs of peritoneal dissemination and distant metastasis. The patient was discharged from the hospital 23 days after the operation, with good postoperative course. Histological diagnosis was pancreatic tail cancer, pT4N0H0P0M(-) fStage IVa. Subsequently, the patient received postoperative adjuvant chemotherapy(TS-1: 100mg/day, 4 courses)combined with Wilms'tumor 1(WT1)peptide-pulsed dendritic cell therapy. No serious adverse events occurred during the postoperative adjuvant therapy. The patient remains alive without recurrence 16 months after the operation.

To clarify the complications associated with subcutaneous central venous access port devices, we investigated the patients who underwent placement of central venous access port devices in our hospital.Overall, 171 cancer patients who underwent placement of subcutaneous central venous access port devices (119 for chemotherapy and 52 for home parenteral nutrition) between February 2006 and December 2011 and who were followed up for 1 month, were retrospectively analyzed in this study. Univariate analysis was performed on complications related to clinical factors, including age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, and use of bevacizumab.The mean follow-up time was 213 days (range, 31-1,873), and 35 patients (20.5%) required the port device to be extracted due to complications, including infection in 24(14.0%), wound dehiscence at the port site in 2 (1.2%), obstruction of the catheter in 6 (3.5%), catheter-induced venous thrombosis in 1 (0.6%), and catheter fracture in 2(1.2%). No statistically significant differences were observed between the frequency of complications and age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, or use of bevacizumab.The incidences of complications related to implantation and management of these devices are relatively high and early. Patients should be followed carefully by chest radiography at regular intervals.

The patient was a 53-year-old woman who underwent colonoscopy for anal pain and melena. We diagnosed her with Stage I (T2N0M0) anal canal squamous cell carcinoma by biopsy specimen and CT scan. We recommended chemo-radiotherapy because she hoped to keep her anus. For this patient, we planned an S-1 administration at a dose of 120 mg/ body/day for consecutive 14 days followed by 7 days of rest period with whole pelvis and bilateral inguinal radiation (total 45 Gy/25 Fr). Then we added a booster radiation (14 Gy/7 Fr) to a local area for 5 days followed by 2 days of rest period. After 2 weeks of chemo-radiotherapy, we could not detect any tumors by colonoscopy. We diagnosed it as a pathological complete response for biopsy specimen.

CASE 1: A 61-year-old man having advanced gastric cancer was presented with massive hematemesis. We could not control bleeding by gastrointestinal endoscopic hemostatic therapy, so we performed a transcatheter arterial embolization (TAE). We performed embolization on the left gastric artery. CASE 2: A 58-year-old man having advanced gastric cancer was presented with hematemesis. We could not control bleeding by gastrointestinal endoscopic procedure, so we conducted TAE. We performed embolization on the left gastric artery and right gastric artery. In both cases, hemostasis was achieved by TAE, and effectively controlled the bleeding from advanced gastric cancer.

A 41-year-old man who had non-small cell lung cancer invading his right 3rd, 4th and 5th ribs with hilum lymph node swelling(cT3N1M0, cStage III A), received chemoradiation therapy, cisplatin(CDDP)/docetaxel, and 2 Gy/Fr of irradiation prior to surgery. But the therapy was discontinued due to interstitial pneumonitis on day 24, during 28 Gy of radiation. At that time, a PET-CT scan revealed the accumulation of FDG in the primary tumor, hilar lymph node, and one of the ipsilateral axillar lymph nodes, in which cancer cell presence was proven by aspiration needle cytology. We organized a radical operation even though the node status was classified to cStage IV, because ipsilateral axillary lymph nodes may be regarded as regional nodes for tumors invading the chest wall. Right upper lobectomy and chest wall resection were performed, and the ipsilateral hilar, mediastinal, and axillary lymphnode were dissected. Pathological findings showed no active cancer cell in the primary lesion and hilar lymph nodes(Ef. 3), but obvious metastasis in one of the axillary lymph nodes(pT0N0M1b, pStage IV). The patient received adjuvant chemotherapy(CDDP/vinorelbine), and is alive and tumor-free 10months after the resection.

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

A 75-year-old female presented with appetite and weight loss and epigastralgia. CT revealed a primary gallbladder carcinoma Stage IVb with multiple hepatic metastases. Gastrofiberscopy revealed an invasion to duodenal and bleeding from the tumor. For her poor performance status, it seems to be too difficult to undergo a general chemotherapy. So after gastrojejunostomy, transarterial embolization (TAE) was performed. She underwent 2 times TAE. There was a notable reduction in tumor size. But pulmonary metastases were found in bilateral lung. She died after 8 months. TAE may be useful for advanced gallbladder carcinoma with tumor vascularity.

We analyzed a treatment outcome and the effect of systemic chemotherapy for patient with unresectable gallbladder carcinoma. Sixteen patients were investigated. Gemcitabine (GEM) was administrated for fifteen patients as the first-line chemotherapy. S-1 was administrated for ten patients as the second-line chemotherapy. The response rate and tumor control rate of the first-line GEM were 14.3% and 78.6%, respectively. The median progression free time of the first-line GEM was 6.0 months. The response rate and tumor control rate of the second-line S-1 were respectively 20.0% and 30.0%. The median progression free time of the second-line S-1 was 1.8 months. The median survival time of all cases was 14.9 months. The outcome of systemic chemotherapy for patients with unresectable gallbladder carcinoma in our hospital was feasible compared with past reports.