[Eight Cases of Catheter Fracture in Internal Jugular Vein Ports for Breast Cancer Chemotherapy].

Subcutaneous implantable venous ports were placed in 414 patients between April 2016 and August 2021 for the purpose of breast cancer chemotherapy in our hospital. Although the internal jugular vein approach was selected to prevent fractures caused by pinch-off syndrome, catheter fracture occurred in 8 patients(1.9%). All patients were ADL-independent women aged 44-62 years(median, 50.5 years). The intravenous ports were placed on the side of the dominant and non-dominant hands in 4 and 4 patients, respectively. Six patients received perioperative chemotherapy, while 2 had advanced breast cancer. Catheter fractures occurred 17.7-54.2 months(median, 41.7 months)after placement. The fractures were discovered when the patients presented with one or more of the following conditions: poor backflow of blood (n=4), subcutaneous emphysema observed on CT(n=1), subcutaneous leakage of CT contrast media(n=3), and no sign or symptom(n=1). The fractures occurred in the clavicular subcutaneous part in all patients. Partial and complete fractures of the catheter occurred in 5 and 3 patients, respectively. In 3 patients with complete fracture of the catheter, catheter tips had strayed into the right atrium and were removed using percutaneous endovascular procedures.

[Correction and apology.]

Removal of published articles. [A Case Report of P0CY1 Gastric Cancer Achieved Long-Term Survival after Treated with Ramucirumab Monotherapy] Masaru Udagawa, Rama Adikrisna, Yoshimi Yamasaki, Akira Ito, Kenta Kobayashi, Megumu Enjoji, Susumu Kirimura. The article was published in Gan to kagaku ryoho, Vol. 47, No. 13. The authors have requested that the article be removed due to the request of the data provider.

[Long-Term Survival of a Patient with Advanced Recurrent Rectal Cancer Treated with a Multidisciplinary Therapy including Five Operations-A Case Report].

A 68-year-old female with rectal cancer underwent low anterior resection with regional lymph node dissection. The final pathological diagnosis was Stage Ⅲa, and an adjuvant therapy(S-1)was provided for 6 months. One year after the surgery, an anastomotic recurrence was detected. Therefore, pelvic chemoradiotherapy with folinic acid and 5-fluorouracil(FL)was provided, and resection was performed with the Hartmann procedure. Following the second surgery, chemotherapy with bevacizumab(BV)and capecitabine plus oxaliplatin(CapeOX)was provided, and the patient showed no signs of recurrence for several years. However, lung metastasis appeared, which was resected. A year later, the patient underwent hepatectomy and radiofrequency ablation for liver metastasis. Another year later, she underwent lung resection again because of new lung metastasis. During the periods between the surgeries, various chemotherapy regimens were followed continuously, however, the patient died of progressive recurrence 8 years and 4 months after the initial surgery. Recurrences and distant metastases are poor prognostic factors for rectal cancers. However, combined effective chemotherapy and radiotherapy with surgery may improve the patient's chances of survival.

[A Case Report of Gastric Cancer Excised after Neoadjuvant Chemotherapy and Long-Term Survival Achieved after NivolumabAdministration for Peritoneal Dissemination].

The patient was a 64-year-old man with Type 3 advanced cancer in the upper body of the stomach. The preoperative tumor marker value of CA19-9 was abnormally high, but there was no proof of distant metastasis or peritoneal dissemination. The first operation was an exploratory laparotomy due to direct tumor invasion to the pancreas. Systemic chemotherapy was performed for tumor reduction. First, S-1 plus cisplatin therapy was administered for 4 courses but discontinued because of renal dysfunction and thrombocytopenia. In the second-line therapy, ramucirumabplus paclitaxel therapy was administered for 7 courses. Since the tumor invasion to the pancreas turned to be clear based on a CT scan, total gastrectomy with regional lymphadenectomy was performed. However, 5 months after surgery, a single nodule appeared in the upper abdomen that was suspected to be peritoneal dissemination. Nivolumab therapy was administered for 16 months without tumor enlargement or any adverse effect. Recently, there has been a marked development in chemotherapy for gastric cancer. Unresectable cases became operable after the administration of appropriate chemotherapy. In our case, nivolumab therapy had no adverse effect. However, serious adverse effects have been reported by several authors which suggests that regular examinations for interstitial pneumonia, hypothyroidism, and other adverse effects are important.

[A Case Report of P0CY1 Gastric Cancer Achieved Long-Term Survival after Treated with Ramucirumab Monotherapy].

The patient was a woman in her early 60s with type 4 advanced cancer which spread throughout the entire stomach. Total gastrectomy with regional lymphadenectomy was performed. She was diagnosed as Stage Ⅳ scirrhous gastric cancer with positive lavage cytology pathologically without any macroscopic peritoneal metastasis(P0CY1). S-1 plus cisplatin therapy was carried out as first-line therapy, but must be stopped after 2 courses because of appetite loss. As the second-line, ramucirumab monotherapy was administered, due to the patient's denial of alopecia and numbness as side effects of paclitaxel. Tumor marker value of CA19-9 remained high 24 months after ramucirumab chemotherapy, but gradually decreased near the normal level with no proof of distant metastasis or peritoneal dissemination. However, after 74 courses, CA19-9 value was elevated and peritoneal dissemination was detected from CT scan. Nivolumab therapy was started as third-line, but only for 5 courses because of indefinite complaints. Afterwards, no chemotherapy has been performed as the patient's request until almost 5 years after surgery. The prognosis of patients with P0CY1 gastric cancer is generally poor, but in our case long-term survival was obtained from ramucirumab therapy only. Recently, ramucirumab monotherapy is administered for advanced HCC patients and expect to be effective in AFP producing gastric cancer. There is an urgent need to elucidate potential predictive biomarkers of ramucirumab efficacy.

[A Case Report of Gastric Cancer with Positive Peritoneal Lavage Cytology and Metachronous Schnitzler's Metastasis Treated with Multimodality Therapy].

A69 -year-old male patient with type 3 gastric cancer in pyloric antrum underwent distal gastrectomy with regional lymphadenectomy. Serosal infiltration of cancer tissue was found in the anterior wall of antrum, and the evaluation of peritoneal lavage cytology were positive. Pathological analysis showed the tumor was mainly consist of moderately tubular adenocarcinoma and strongly positive for HER2 stain. Postoperatively, combined therapy of capecitabine and trastuzumab was carried out, but cisplatin was excluded because of the patient's rejection. However, nine months after drug withdrawal, singular tumor located at left anterior side of rectum was detected by abdominal CT scan. Colonoscopy revealed its mucosal invasion and the result of biopsy was metastasis of gastric cancer, also known as Schnitzler's metastasis. Local radiation therapy aimed at the tumor was performed, followed by capecitabine and oxaliplatin therapy for 18 months. After the therapy, Schnitzler's metastatic lesion was disappeared and biopsy from colonic mucosa revealed there was no tumor tissue left. The patient has been in good health 5 years after surgery. This case suggests that multimodality therapy including radiation and chemotherapy might improve survival of gastric cancer patient with positive peritoneal lavage cytology and metachronous metastasis.

[Recurrence of a Giant Retroperitoneal Leiomyosarcoma Six Years after the Initial Surgery].

A 51-year-old man came to our department because of a large abdominal mass. CT, MRI, and sonography revealed a large tumor adjacent to the retroperitoneal area. A resection was performed, and histologically we confirmed the diagnosis as a leiomyosarcoma originating from the retroperitoneum. Six years after the initial surgery, the patient came to our outpatient department with a complaint of nausea. A relatively large tumor was seen on a CT scan that was causing obstruction of the duodenum. Another surgery was performed with the final diagnosis as a recurrence of the leiomyosarcoma. After 3 courses of adjuvant chemotherapy with eribulin, the patient presented with abdominal distension. CT revealed a very large tumor with massive invasion to the ileum and colon. This time, we considered the tumor unresectable, and administered chemotherapy with a combination of doxorubicin and ifosfamide. However, after 1 course, the patient's condition worsened and he died of the disease 3 months after the chemotherapy.

[A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases.

[A Case of Squamous Cell Carcinoma of the Anal Canal with a Perianal Abscess].

A 72-year-old female patient was referred to our department because she felt pain at the anus with pus discharge. Physical examination revealed a tumor on the left side of the anus, and a subcutaneous induration near the tumor. Abdominal CT scan revealed an irregularly shaped tumor with abscess formation. There were no enlarged lymph nodes or distant metastasis. Anal canal carcinoma (cStage Ⅱ) with a complication of perianal abscess was suspected, so we performed surgical incision and drainage. A biopsy of the tumor led to the diagnosis of squamous cell carcinoma. However, because surgical drainage alone was not effective for treatment of the abscess, colostomy of the sigmoid colon was carried out 14 days after admission. After chemoradiation therapy (5-FU 800 mg/m2/day on days 1-4 and 29-32, mitomycin C [MMC] 10 mg/m2 on days 1 and 29, and radiation with a total dose 54 Gy), the tumor disappeared completely, considered to be a complete response. Twenty months after chemoradiation, there were no signs of recurrence.

Intratumoral injection of BCG-CWS-pretreated dendritic cells following tumor cryoablation.

Intratumoral administration of dendritic cells (DC) following cryoablation of tumor is one of the personalized cancer immunotherapies which is able to induce immune responses to multiple endogenous tumor antigens, including shared and unique antigens. Here we describe protocols of cryoablation of tumors, generation of cultured DC, pretreatment of DC with a Toll-like receptor (TLR)-stimulating purified component of Bacillus Calmette-Guerin cell wall fraction (BCG-CWS) and highly immunogenic keyhole limpet hemocyanin (KLH) antigen, and combined use of tumor cryoablation and intratumoral administration of BCG-CWS-pretreated DC in both a murine model and cancer patients.

Effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases.

OBJECTIVES: The staging system of the International Union Against Cancer considers tumor deposits to be N1c in patients with no regional lymph node metastasis, but the significance of tumor deposits in patients with regional lymph node metastases is unclear. We investigated the effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases. PATIENTS AND METHODS: From 2000 to 2008, 551 patients underwent resections for colorectal cancer at our medical center. We excluded 87 patients who had distant metastases or had received neoadjuvant chemotherapy or radiotherapy from our study and statistically analyzed the remaining 464 patients. RESULTS: Stepwise multivariate Cox proportional hazards analysis in patients with regional lymph node metastases showed only tumor deposits to be significant for overall survival (hazard ratio: 2.813; P = 0.0002). Recurrence was seen in 49.2% of patients with tumor deposits (30/61) compared with 14.4% of patients without them (58/403; P < 0.0001). Tumor deposits did not show the same effect on overall survival as lymph node metastases. CONCLUSIONS: Tumor deposits were significantly associated with poorer overall survival in colorectal cancer patients with regional lymph node metastases. The effect of tumor deposits on overall survival was between that of lymph node metastasis and distant metastasis.

[Two cases of ileocecal carcinoid found by total colonoscopy and a review of the literature on 16 cases].

We report 2 cases of ileocecal carcinoid with review of the literature recently reported in Japan. Both cases were diagnosed as carcinoid by colonoscopic biopsy after ileocecal tumors had been pointed out by computed tomography. We performed curative operation with lymph node dissection. Since multiple lymph node metastases were shown in both cases pathologically, they were closely followed after surgery, but no recurrence has been shown. Since SSTR2a stain was strongly positive in both cases, octreotide, the effectiveness of which was verified in the PROMID study might be administered if necessary. As ileocecal carcinoid has a tendency to metastasize to other organs, careful surveillance by colonoscopy and early detection are required. Furthermore, development of effective drugs following octreotide and further investigation including biological and histopathological analysis of neuroendocrine tumors including carcinoid are necessary.

Dendritic cell based personalized immunotherapy based on cancer antigen research.

Human tumor antigens were identified using various immunological and genetic methods, and immune responses to the identified antigens were evaluated in cancer patients. Autologous tumor specific unique antigens derived from genetic alterations in cancer cells were isolated from patients with favorable prognosis after immunotherapy, indicating that they are attractive targets for immunotherapy. Immunogenicity of shared antigens was found to differ among patients due to antigen expression in cancer cells and patients' immunoreactivity. These observations suggest that personalization may be applied for cancer immunotherapy. We therefore developed intratumoral DC administration protocols that are able to induce immune responses to both unique and shared tumor antigens expressed in each individual cancer. By combining cryoablative tumor pretreatment and TLR stimulated DC, the anti-tumor effect of the intratumoral DC administration was significantly augmented in a murine tumor model. This improved protocol enhanced systemic induction of anti-tumor CD8+ CTL, and was able to regress relatively large remote untreated tumors. In clinical trials, systemic immune induction was observed by intratumoral DC administration following cryoablative tumor treatment, although anti-tumor effects are relatively weak, indicating that additional interventions are required for more effective immunotherapy.

Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation.

PURPOSE: We developed an effective immunotherapy, which could induce antitumor immune responses against shared and unique tumor antigens expressed in autologous tumors. EXPERIMENTAL DESIGN: Intratumoral administration of dendritic cells is one of the individualized immunotherapies; however, the antitumor activity is relatively weak. In this study, we attempted to enhance the antitumor efficacy of the i.t. dendritic cell administration by combining dendritic cells stimulated with Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) additionally with cryoablative pretreatment of tumors and analyzed the therapeutic mechanisms. RESULTS: These two modifications (cryoablation of tumors and BCG-CWS stimulation of dendritic cells) significantly increases the antitumor effect on both the treated tumor and the untreated tumor, which was distant at the opposite side, in a bilateral s.c. murine CT26 colon cancer model. Further analysis of the augmented antitumor effects revealed that the cryoablative pretreatment enhances the uptake of tumor antigens by the introduced dendritic cells, resulting in the induction of tumor-specific CD8(+) T cells responsible for the in vivo tumor regression of both treated and remote untreated tumors. This novel combination i.t. dendritic cell immunotherapy was effective against well-established large tumors. The antitumor efficacy was further enhanced by depletion of CD4(+)CD25(+)FoxP3(+) regulatory T cells. CONCLUSIONS: This novel dendritic cell immunotherapy with i.t. administration of BCG-CWS-treated dendritic cells following tumor cryoablation could be used for the therapy of cancer patients with multiple metastases.

Investigation into the usefulness and adverse events of CDDP, 5-fU and dl-leucovorin (PFL-therapy) for advanced colorectal cancer.

Biochemical modulation of 5-fluorouracil (5-FU) has been verified the evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. We investigated the therapeutic and adverse drug reaction of intensive chemotherapy using cisplatin (CDDP), 5-FU and dl-leucovorin (LV) (PFL-therapy), which may be producing dual biochemical modulation effect of 5-FU for advanced colorectal carcinoma. Administration schedule was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days. This regimen was repeated at 3-week intervals in hospital. Sixteen patients were enrolled in this study, most of whom had a history of previous chemotherapy as adjuvant treatment, and the response rate was 25%, with four patients having "partial response" and eight "no change". In respect to performance status, 46% of patients who completed the protocol were markedly improved in spite of their poor performance status before treatment. Moreover, when patients were classified into two groups based on changes of the serum level of CEA, "responder in CEA level" showed better prognosis than "non-responder in CEA level". Major toxicities were nausea, hyperglycemia and neutropenia. Three patients experienced Grade 4 hematological side effect, but these complications resolved quickly in all patients except for one patient. PFL-therapy is effective for advanced colorectal cancer with large tumor burden and showed the same prognostic result as the American and European trials in spite of smaller number of treatment cycles and a history of previous chemotherapy. We will be able to demonstrate the usefulness of this regimen for Japanese patients with advanced colorectal cancers after adding new cases to the present report.