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Purpose The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. Methods This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. Results PFS was superior in group M (median PFS; 8.7 vs. 11.5 months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0 months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6 weeks/course, P = 0.051) in the induction term. Conclusion We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

Guidelines advocate minimal ileal resection when right hemicolectomy is performed for right-sided colon cancer. The practice, thought to prevent malabsorption syndrome, does not appear to foster local recurrence. Little evidence based on rigorous study exists, however. To understand the pattern of lymphatic spread of right-sided colon cancer toward the small bowel and thus determine the appropriate margin size, we prospectively investigated anatomical distribution of lymph nodes (LNs) in the small bowel mesentery and of metastasis to these nodes in patients with right-sided colon cancer treated by such surgery. In each case, the mesenteric specimen, which had been dissected along the ileocolic vessels and included intermediate LNs, was divided into 2 areas: that 0–3 cm from the vessel pedicle (area 1) and that 3–5 cm from the pedicle (area 2). The peri-intestinal mesentery was cut into 9 segments. Ninety-one patients were included in the study. Overall, 3366 LNs were dissected. Four hundred fifty-three of these LNs were located in area 1 (90 cases), and 15 (3.3%) were metastatic. Only 63 LNs were located in area 2 (34 cases; average of 0.69 per patient); none was metastatic. Overall, 269 LNs were found in the small bowel mesentery (in 56 of the 91 patients). Only 4 were positive (3 cases), and all were within 5 cm of the ileocecal valve. Our data indicate that a surgical margin 3 cm from the ileocecal pedicle and a short (5 cm) ileal margin are oncologically reasonable for effective right hemicolectomy.

BACKGROUND: With low anterior resection (LAR) for rectal cancer, the oncologic outcomes are recently good. A diverting ileostomy is often created to protect the newly constructed anastomosis; seldom is a permanent stoma needed. Predicting postoperative anorectal function remains difficult, however. We speculated that the endoscopic appearance of the anastomosis before ileostomy closure is predictive of the post-operative anorectal function and tested our hypothesis retrospectively. METHODS: Included in the study were 80 patients who, between September 2014 and August 2017, underwent LAR at Kanagawa Cancer Center. A diverting stoma had been created during the primary surgery, and ileostomy closure was performed about 6 months later. The anastomosis was examined endoscopically just before ileostomy closure, and the features were scored by two well-trained endoscopists. Daily defecation frequency and incontinence (Kirwan Score) were assessed after closure through physician-patient interview, and correlation between endoscopic feature scores and these measures of anorectal function was tested. RESULTS: Documented endoscopic features included erythema in 79% of patients, erosion (45%), ulceration (5%), granulomatous change (41.3%), granular protrusions (17.5%); hemorrhagic (20.0%) or white-coated (30.0%) mucosa. Anastomosis stricture

The effectiveness of lymph node dissection tends to be reduced clinically in elderly patients with colorectal cancer because of physical limitations, such as comorbidities and organ dysfunction. We investigated the influence of the level of lymph node dissection on the prognosis of elderly patients with colorectal cancer. A total of 137 patients with pT2 or more-advanced tumors or lymph node metastasis were retrospectively studied. The 5-year overall survival(OS)andrelapse free survival(RFS) rates were 74.1% and 63.9%, respectively. Lymph node dissection was an independent prognostic factor in the examination of prognostic factors of OS. In the propensity-matchedcohort, the 5-year OS rates were 87.2% and5 8.2%(p=0.02), and the 5-year RFS rates were 77.8% and4 6.4%(p=0.03)in the D3 andred ucedgroups, respectively. The D3 group hada significantly better prognosis than the reduced group. D3 lymph node dissection might contribute to the improvement of prognosis in elderly people with colorectal cancer.

A 64-year-old woman was diagnosed with Stage IV gastric cancer with lymph node and multiple liver metastases. She was treated with 6 courses of chemotherapy, in 3-week courses, with capecitabine (1,000 mg/m/(2)) plus cisplatin(80 mg/m(2)) administered for 2 weeks, followed by a drug-free week. She underwent curative total gastrectomy with D2 lymph node dissection and reconstruction by using the Roux-en-Y method. The postoperative pathological findings revealed a T3 (SE), N1M1, Stage II B tumor; the tumor was determined to be Grade 1b owing to the chemotherapeutic effect. Postoperatively, only S-1 therapy was administered, because of the development of Grade 3 hand-foot syndrome. The patient is alive 1 year and 8 months after the initial gastrectomy.

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1', 2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized starting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 microg/mL against HSV-1 Tomioka vs 0.81 microg/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

Chlorohydroxylation d'olefines non fonctionnalisees en utilisant soit l'hydroperoxyde de t-butyle soit le peroxyde de di-t-butyle en presence de TiCl 4 . Stereoselectivite

Ribavirin (l-β-D-ribofuranosyl-l, 2, 4-triazole-3-carboxamide; Virazole®), which is known as a potent antiviral agent, was synthesized directly from purine nucleosides and l, 2, 4-triazole-3-carboxamide (TCA) by a newly selected bacterium, Brevibacterium acetylicum ATCC 954. Among the purine nucleosides tested, guanosine and xanthosine were selected as the best substrates as to ribavirin production. The highest amount of ribavirin produced was 229 mM from 300 mM guanosine and 300 mM TCA on 96 hr reaction at 60°C. In this system involving ATCC 954, ribavirin was effectively even produced at a limited concentration of phosphate (about 10mM). ATCC 954 could also produce ribavirin directly from inosine and TCA in a high yield, but could hardly produce it directly from adenosine and TCA. In contrast, a bacterium belonging to the genus, Bacillus, could produce ribarivin directly from adenosine and TCA in a high yield.