Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. METHODS: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. RESULTS: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW. CONCLUSIONS: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).

Efficacy of Ninjin'yoeito in treating severe coronavirus disease 2019 in patients in an intensive care unit.

Coronavirus Disease-2019 (COVID-19), an infectious disease associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global emergency with high mortality. There are few effective treatments, and many severe patients are treated in an intensive care unit (ICU). The purpose of this study was to evaluate whether the Japanese Kampo medicine ninjin'yoeito (NYT) is effective in treating ICU patients with COVID-19. Nine patients with confirmed SARS-CoV-2 infection admitted to the ICU were enrolled in this study. All patients underwent respiratory management with invasive mechanical ventilation (IMV) and enteral nutrition. Four patients received NYT (7.5 g daily) from an elemental diet tube. We retrospectively examined the prognostic nutritional index (PNI), length of IMV, length of ICU stay, length of hospital stay, rate of tracheostomy, and mortality rate. The median age of the enrolled participants was 60.0 years (4 men and 5 women). The median body mass index was 27.6. The most common comorbidity was diabetes (4 patients, 44%), followed by hypertension (3 patients, 33%) and chronic kidney disease (2 patients, 22%). The median length of IMV, ICU stay, and hospital stay were all shorter in the NYT group than in the non-NYT group (IMV; 4.0 days vs 14.3 days, ICU; 5.3 days vs 14.5 days, hospital stay; 19.9 days vs 28.2 days). In the NYT and non-NYT groups, the median PNI at admission was 29.0 and 31.2, respectively. One week after admission, the PNI was 30.7 in the NYT group and 24.4 in non-NYT group. PNI was significantly (p = 0.032) increased in the NYT group (+13.6%) than in the non-NYT group (-22.0%). The Japanese Kampo medicine NYT might be useful for treating patients with severe COVID-19 in ICU. This study was conducted in a small number of cases, and further large clinical trials are necessary.

[A Case of Double Colorectal Cancer Diagnosed by Preoperative CT Colonography].

A 66‒year‒old man was admitted to our hospital because of anemia and a positive fecal occult blood test in the medical examination. Colonoscopy revealed a type 2 advanced sigmoid colon cancer with circular stenosis. Computed tomography (CT)colonography was performed to examine the oral colon. The apple core signs were found both in the sigmoid and transverse colon. We diagnosed a double colon cancer and performed a laparoscopic left hemicolectomy and sigmoidectomy. The tumor was histopathologically diagnosed as a multiple cancer including a transverse and a sigmoid colon cancer. Although evaluations of the intestine for colon cancer with stenosis are performed by enema examination or endoscopic examination after colon stent placement, both examinations are invasive. CT colonography is considered to be a minimally invasive and an effective preoperative examination for colorectal cancer with stenosis.

Multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine: A case report.

FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life.

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 Advanced Hepatocellular Carcinoma Successfully Treated with Liver Resection after Administration of Sorafenib].

CASE: A 76-year-old man was referred to our hospital for advanced hepatocellular carcinoma(HCC)with chronic hepatitis type B. Although he underwent right anterior sectionectomy and S3 segmentectomy, multiple recurrences were found in the hepatic remnant after 2 months. Transcatheter arterial chemoembolization(TACE)and transcatheter arterial infusion (TAI)were performed separately. One and a half month after the last TAI, AFP and PIVKA-Ⅱ levels markedly elevated, and multiple early enhancing nodules with portal vein tumor thrombosis were detected on CT. A half dose of sorafenib(400mg/ day)was administered to the patient who was refractory to TACE. Sorafenib was discontinued after 4 weeks because the patient developed general fatigue and anorexia(Grade 3). Furthermore, these adverse events became worse, and ascites appeared. He was hospitalized in the palliative care unit for best supportive care for 3 weeks and also received outpatient treatment for more than 14 months. Fifteen months after discontinuing sorafenib administration, his condition improved dramatically, and CT revealed that the multiple HCC had reduced in size. Moreover, the portal vein tumor thrombosis disappeared. As his performance status and liver function were well preserved, he underwent partial hepatectomy for residual HCC. The patient remains alive without recurrence at 18 months, despite no administration of sorafenib. CONCLUSION: This case demonstrates that sorafenib administration combined with surgical treatment could possibly cure advanced HCC refractory to TACE.

Cervical chylous leakage following esophagectomy that was successfully treated by intranodal lipiodol lymphangiography: a case report.

BACKGROUND: Chylous leakage is a well-known complication after esophagectomy, but cervical chylous leakage is relatively rare, and considerable controversy remains regarding the appropriate management strategies. We herein report a case of cervical chylous leakage treated successfully by lipiodol lymphangiography. CASE PRESENTATION: The patient, a 70-year-old man with middle thoracic esophageal cancer, underwent radical esophagectomy with 3-field lymph node dissection and subsequently developed cervical chylous leakage. From the second postoperative day (POD2), the amount of fluid in the cervical drainage tube increased by 200-300 ml/day. We started octreotide (300 µg/day) on POD5 and etilefrine (120 mg/day) on the POD6. However, the amount of cervical discharge did not decrease. We performed lipiodol lymphangiography on POD8. Thereafter, the amount of cervical discharge finally began to decrease. We removed the drainage tube on POD13, and the patient was discharged from the hospital on POD23. CONCLUSIONS: Our case suggests the clinical efficacy of lipiodol lymphangiography for cervical chylous leakage after esophagectomy.

Treatment Rationale and Study Design for Clinical Trial on the Efficacy of UFT/LV for Stage II Colorectal Cancer With Risk Factors for Recurrence (JFMC46-1201).

BACKGROUND: The usefulness of adjuvant chemotherapy for stage II colon cancer has not been established. Meanwhile, the presence of stage II colon cancer with high-risk factors for recurrence has been reported. To our knowledge, no prospective study of adjuvant chemotherapy for stage II colon cancer with high-risk factors has been implemented to date. PATIENTS AND METHODS: This study is a prospective nonrandomized controlled study based on patients' selection of treatment option, including randomized therapeutic decision-making, to evaluate the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) with leucovorin (LV) for stage II colon cancer with high-risk factors for recurrence, compared with surgery alone. Five courses of UFT/LV therapy will be given as follows: UFT (300 mg/m(2)/d) with LV (75 mg/d) will be orally administered in 3 doses per day. Treatment will be received daily for 28 days, followed by a 7-day rest or will be received daily for 5 days, followed by a 2-day rest. For both regimens, 1 course will last 5 weeks, and 5 courses will be given. The primary end point is disease-free survival. A propensity score matching will be conducted based on 7 variables that represent risk factors to minimize selection bias in a comparison between the nonrandomized arms. For this nonrandomized comparison, a target sample size is set at 1200 (400 and 800 patients for the surgery alone and UFT/LV groups, respectively) and 1720 patients will be enrolled. In this study we aim to evaluate the therapeutic usefulness of adjuvant chemotherapy with UFT/LV for stage II colorectal cancer with risk factors for recurrence.

[A Patient with Recurrent Ulcerative Colitis-Associated Rectal Cancer Attaining a Complete Response with FOLFIRI plus Bevacizumab].

A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

Maintenance of the nutritional prognostic index predicts survival in patients with unresectable metastatic colorectal cancer.

PURPOSE: Nutrition and immunity significantly affect the progression of cancer in cancer patients. Therefore, the evaluation of the nutritional and immune status would be useful as a prognostic factor and to determine the optimal treatment strategy for patients with unresectable metastatic colorectal cancer who are receiving chemotherapy. The aim of this retrospective study was to evaluate the prognostic significance of the nutritional and immune status in patients with unresectable metastatic colorectal cancer treated with chemotherapy. METHODS: We retrospectively reviewed 80 patients with colorectal cancer. A total of 22 patients had metachronous unresectable cancer, and 58 patients had synchronous unresectable cancer. All patients underwent combination chemotherapy with oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin as first-line chemotherapy. We then examined the correlations between the Onodera's prognostic nutritional index (OPNI) and the patients' clinicopathological features. The OPNI was calculated as follows: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). According to the receiver operating characteristic (ROC) curve analysis, the cutoff value for OPNI was 44.5. RESULTS: Patients with a pretreatment OPNI of ≧44.5 demonstrated a longer OS than those with a pretreatment OPNI of <44.5. Moreover, we categorized these patients into four groups according to the combination of the pre- and post-treatment OPNI. The patients in the group with both OPNIs ≥44.5 exhibited a better prognosis compared to the other group (p = 0.001). CONCLUSION: The OPNI is considered to be a useful marker for predicting the long-term outcome in patients who receive chemotherapy for unresectable metastatic colorectal cancer.

[Promising effects of pregabalin in the treatment of oxaliplatin-induced sensory neuropathy in patients with colorectal carcinoma].

Thirteen patients with metastatic colorectal cancer who suffered from oxaliplatin-induced sensory neuropathy were evaluated to determine the neuropathy Grade before and after the administration of pregabalin. All patients received oxaliplatin as adjuvant or first-line chemotherapy. The mFOLFOX6 and CapeOX groups included 3 and 10 cases, respectively, and the average treatment regimens were 8 and 5 doses, respectively. Before receiving pregabalin, sensory neuropathy was classified as Grade 3 in 2 patients, as Grade 2 in 8 patients, and as Grade 1 in 3 patient. The average amount of pregabalin administered to patients was 237 (range: 150-450) mg. After administering pregabalin, we observed improvements in 8 neuropathy cases (61. 5%)within approximately 2 weeks. All side effects were mild. In this study, pregabalin was shown to positively impact sensory neuropathy resulting from oxaliplatin treatment and to enable the long-term use of oxaliplatin-based chemotherapy.

[Survey of integrated medical care for dementia in Hyogo Prefecture: comparison in two areas].

OBJECTIVE: To assess the attitude of medical care for dementia among the primary care physicians (PCP) in two different areas in Hyogo Prefecture and compare it. METHODS: A 15-item questionnaire related medical care for dementia was developed and sent it by mail to the PCP in December, 2011. RESULTS: One area is an urban area and the other is a rural area. The response rates were 42.9% and 36.7%, respectively. The rate of the PCP in the urban area who was interested to care dementia elderly was higher, compared to the rural area. The integrated medical care net work was well functioning in the urban area. The rate of PCP in the urban area who wanted to have training for dementia care was higher than in the rural area. CONCLUSIONS: Although the rate of elderly in the population in the rural area is higher, the PCP in the rural area seemed not to be interested in dementia care.

A meta-analysis of the short- and long-term results of randomized controlled trials that compared laparoscopy-assisted and conventional open surgery for rectal cancer.

PURPOSE: We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopy-assisted and open rectal surgery for the treatment of patients with rectal cancer. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and the Cochrane Controlled Trial Register for relevant papers published between January 1990 and April 2011 by using the search terms "laparoscopy," "laparoscopy assisted," "surgery," "rectal cancer," and "randomized controlled trials." We analyzed outcomes over short- and long-term periods. RESULTS: We identified 12 papers reporting results from randomized controlled trials that compared laparoscopic surgery with open surgery for rectal cancer. Our meta-analysis included 2,095 patients with rectal cancer; 1,096 had undergone laparoscopic surgery, and 999 had undergone open surgery. In the short-term period, 13 outcome variables were examined. In the long-term period, eight oncologic variables, as well as late morbidity, urinary function, and sexual function were analyzed. Laparoscopic surgery for rectal cancer was associated with a reduction in intraoperative blood loss and the number of transfused patients, earlier resumption of oral intake, and a shorter duration of hospital stay over the short-term, but with similar short-term and long-term oncologic outcomes compared to conventional open surgery. CONCLUSIONS: Laparoscopic surgery may be an acceptable alternative treatment option to conventional open surgery for rectal cancer.

[A case report of advanced rectal cancer showing a pathological complete response by neo-adjuvant FOLFOX chemotherapy].

A 72-year-old man was admitted with melena. Colonoscopy detected an advanced rectal cancer. CT scan revealed the prostate was invaded. We decided to start a systemic chemotherapy (mFOLFOX6). The chemotherapy (mFOLFOX6) was performed six times. After the treatment with chemotherapy, the tumor shrunk. Abdominoperineal resection of rectum was done, and a final pathological examination revealed a complete response of the main tumor.

[The outcome of chemotherapy by sorafenib in advanced hepatocellular carcinoma].

We analyzed the treatment outcome and effect of sorafenib in advanced hepatocellular carcinoma. Nine patients were received the therapy of sorafenib between June 2009 and October 2009. The overall incidence of treatment-related adverse events was 87.5%. Grade 3 drug-related adverse events included a hand-foot skin reaction (two patients) and fatigue (one patient). Grade 2 hypertension (three patients), grade 1 diarrhea (two patients) and anorexia (four patients) occurred at this study. The response rate was 0% (CR/PR 0, SD 2, PD 6) and median overall survival length was 101 days. Now there are two patients undergoing the therapy of sorafenib. Effect of sorafenib in advanced hepatocellular carcinoma was not good in this study, and drug-related adverse events had a high rate. However, the continuous treatment was possible with dose modified chemotherapy.

[Results of neo-adjuvant chemotherapy by FOLFOX and FOLFIRI for colorectal liver metastasis].

We analyzed a treatment outcome and the effect of FOLFOX and FOLFIRI neo-adjuvant chemotherapy (NAC) for patient with liver metastasis of colorectal cancer. Eleven patients undergoing hepatectomy after NAC were investigated. FOLFOX was performed for 8 patients, and FOLFIRI was for 3 patients. The response rate was 45.5% (PR 5, SD 6), and the reduction rate was 37.7%. The average ICG R15 value before hepatectomy was 13.7%. A complication during and after operations was not recognized. The average observation period was 19.8 months (8-45 months). Now, 9 patients are alive with no recurrence. NAC by FOLFOX for liver metastasis of colorectal cancer showed a high reduction rate, and there was a little influence to hepatectomy indicating that FOLFOX could be an effective therapy.