Long-Term Follow-up Data of a Multi-Institutional Phase-2 Study of S-1/oxaliplatin and Bevacizumab Therapy in Patients with Advanced Colorectal Cancer: The HiSCO-02 Study

Oral fluoropyrimidines (FUs) have certain advantages over intravenous FUs, such as longer intervals between outpatient visits, no requirement for central venous port (CVP) implantation, and lower incidence of neutropenia. We previously reported the efficacy of S-1/oxaliplatin (SOX) with bevacizumab therapy as a first-line treatment for advanced colorectal cancer (CRC) in a prospective phase-II multi-institutional clinical trial (HiSCO-02 study). However, our prognostic data at the time lacked a sufficient observation period. Herein, we analyze the longer-term follow-up data, focusing on the status of eventual CVP implantation via an open-label, non-randomized, multicenter study. This study enrolled 55 patients (mean age, 64 years), of whom 43 died (41 of primary cancer). The median overall survival was 22.7 months (95% CI: 20.1-34.7 months). Post-treatment regimens after failure of first-line treatment were initiated in 43 patients; CPT11-based regimens were selected in most cases, and other oral FU combinations in nine. CVP was implanted in 35 patients prior to first-line treatment; eleven of the remaining 20 patients did not require CVP implantation. In conclusion, we report here the final prognostic update of the Phase II clinical trial examining the efficacy of SOX plus bevacizumab therapy, the results of which confirm the clinical efficacy of this regimen

Toxicity Assessment of the Xanthid Crab Demania cultripes from Cebu Island, Philippines

Several cases of poisoning resulting in human fatalities and stemming from the ingestion of coral reef crabs have been reported from the Indo-Pacific region. We assessed the toxicity of the unidentified xanthid crab collected from the Camotes Sea off the eastern coast of Cebu Island, central Visayas region of Philippines from the food hygienic point of view. All seven specimens, which were identified with Demania cultripes, collected in 2006 were toxic to mice irrespective of the season of collection and induced paralytic symptoms typical of tetrodotoxin (TTX) and paralytic shellfish poison (PSP). The activity was expressed in mouse unit (MU) being defined as the amount of TTX to kill a 20 g ddY male mice in 30 min after i.p. injection. Toxicity scores for viscera and appendages of specimens were 18.2 ± 16.0 (mean ± S.D.) and 4.4 ± 2.6 MU/g, respectively. The highest individual toxicity scores observed for viscera and appendages were 52.1 and 7.7 MU/g, respectively. The frequency of toxic samples was 100%. Toxin profiles as determined by high-performance liquid chromatography-fluorescent detection analysis (HPLC-FLD) revealed that TTX was the main toxic principle accounting for about 90% of the total toxicity along with 4-epi TTX and 4,9-anhydroTTX. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed mass fragment ion peaks at m/z 376, 392 and 407, which were characteristic of the quinazoline skeleton (C9-base) specific to TTX. In addition, only a small amount of PSP containing gonyautoxins1–4 and hydroxysaxitoxin was detected. To our knowledge, this is the first report presenting evidence of occurrence of TTX and PSP in the xanthid crab D. cultripes inhabiting waters surrounding Cebu Island. From food hygienic point of view, people in coastal areas should be warned of the potential hazard of this crab in order to prevent its intentional or accidental consumption

Successful resection of liver metastasis detected by exacerbation of skin symptom in a patient with dermatomyositis accompanied by rectal cancer: a case report and literature review

Abstract Background Dermatomyositis (DM) is a rare syndrome that belongs to the group of idiopathic inflammatory myopathies. The association between DM and malignancy is well recognized, and the severity of DM symptoms has been linked to the progression of metastatic disease. Case presentation We report the case of a 42-year-old man that was diagnosed with dermatomyositis (DM) and rectal cancer. Proctectomy was performed, and DM symptoms were resolved postoperatively. One year and 9\ua0months after the surgery, liver metastasis occurred accompanied by the exacerbation of DM symptom. Partial resection of the liver was performed, and postoperative course was uneventful. DM symptoms improved postoperatively, and no evidence of cancer recurrence or DM symptoms was observed 2\ua0years after the second surgery. To date, few reports have described recurring cases of DM accompanied by colorectal cancer in detail. We reviewed four similar cases that were reported poor prognoses with treatment resistance. However, our case report demonstrates good long-term results with resection of metastatic lesion. Conclusions It is important to check the exacerbation of DM symptoms, as this symptom sometimes preceded cancer relapse during the follow-up of our patient with DM and colorectal cancer

Clinical Significance of Pharmacological Prophylaxis based on the Original Risk Classification of Venous Thromboembolism after Lower Abdominal Surgery

Pharmacological prophylaxis was not routinely administrated following gastroenterological surgery because of concerns about bleeding complications. We tried to establish the original risk classification to determine the indication for pharmacological prophylaxis for selected patients at high risk of venous thromboembolism (VTE). One hundred and fifty-six consecutive patients who underwent lower abdominal elective surgery were divided into three groups (highest, high, and low risk groups) based on the original risk classification. Pharmacological prophylaxis was indicated for patients in the highest and high risk groups. We investigated safety and efficacy of the pharmacological prophylaxis based on this classification. Sixteen patients were classified in the highest, 50 in the high, and 90 in the low risk groups. Pharmacological prophylaxis was used for 59 cases (37.8%). There was no symptomatic pulmonary embolism or major bleeding complications. There were no significant differences in the occurrence of postoperative complications, analgesia use, and median postoperative pain scores for the three groups. In the highest and high risk groups administrated pharmacological prophylaxis, fibrin degradation products (FDP) and D-dimer did not change between postoperative day 1 and day 7. These data suggested the clinical significance of the pharmacological prophylaxis based on the original risk classification

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression

Retroperitoneal abscess complicated with necrotizing fasciitis of the thigh in a patient with sigmoid colon cancer

<p>Abstract</p> <p>Background</p> <p>Necrotizing fasciitis of the thigh due to the colon cancer, especially during chemotherepy, has not been previously reported.</p> <p>Case presentation</p> <p>A 67-year-old man admitted to the hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle. Multiple hepatic metastases were also found, and combination chemotherapy with irinotecan and S-1 was administered. Four months after the initiation of chemotherapy, the patient developed gait disturbance and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high C-reactive protein level. Computed tomography of the abdomen and pelvis showed gas and fluid collection in the retroperitoneum adjacent to the sigmoid colon cancer. The abscess was locally drained under computed tomographic guidance; however, the infection continued to spread and necrotizing fasciitis developed. Consequently, emergent debridement was performed. The patient recovered well, and the primary tumor was resected after remission of the local inflammation.</p> <p>Conclusion</p> <p>Necrotizing fasciitis of the thigh due to the spread of sigmoid colon cancer is unusual, but this fatal complication should be considered during chemotherapy for patients with unresectable colorectal cancer.</p

Establishment of an antiemetic protocol for chemotherapy-induced nausea and vomiting evaluated using the Multinational Association of Supportive Care in Cancer Antiemesis Tool in colorectal cancer

This study aimed to evaluate the frequency and extent of chemotherapy-induced nausea and vomiting (CINV) in patients with colorectal cancer (CRC) who underwent chemotherapy, using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT), and establish an antiemetic protocol for the management of CINV, independent of the treating oncologist. We conducted a prospective observational study from October 2017 to June 2018 at the Higashihiroshima Medical Center. Patients who had undergone moderate CINV risk chemotherapy for CRC were eligible. The incidence of CINV was evaluated using the MAT, and medical prophylaxis was gradually provided following the antiemetic protocol. We enrolled 30 patients, and 27 of 30 patients (90%) were assessed more than once using the MAT. Among these 27 patients, the incidence of acute nausea was 30% and delayed nausea was 26% as evaluated using the MAT based on recommended pharmacological prophylaxis guidelines. Between the start and end of the survey, there was no significant difference in the numeric rating scale (NRS) score for acute nausea, but there was a significant reduction in the NRS score for delayed nausea. The clinical significance of the antiemetic protocol as assessed using the MAT in reducing CINV was demonstrated. The clinical use of the protocol may help in the realization that selective pharmacological prophylaxis for patients with CINV is possible, independent of the treating oncologist