Wataru Kimura

This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m² once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000–1500 mg/m² once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0). Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%. Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32–40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters. STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

Background: For safe laparoscopic gastrectomy, it is essential to secure a good visual field by employing liver retraction. We have developed a safe and easy method for liver retraction using a silicone disc, and evaluated its feasibility. Methods: We analyzed retrospectively 36 patients with gastric cancer, who underwent laparoscopic distal gastrectomy employing liver retraction by a silicone disc and needle forceps (Silicone group) or by the Penrose drain method (Penrose group) between January 2013 and July 2016. The time needed for liver retraction, complications resulting from it, and postoperative liver dysfunction were compared between the two groups. Results: In all patients in both groups, the operation was performed successfully, obtaining an appropriate visual field. The mean time required for liver retraction was 633.8 ± 286.6 seconds in the Silicone group and 639.8 ± 328.6 seconds in the Penrose group ( P = .954 ) . Postoperative elevation of either aspartate transaminase (AST) or alanine aminotransferase (ALT) level was recognized in 13 (72.2%) of the Silicone group patients and 18 (100%) of the Penrose group patients ( P = .0160). The mean AST and ALT levels in the Silicone group were significantly lower than those in the Penrose group on postoperative days 0, 1, and 3. Among intraoperative complications related to liver retraction, hemorrhage from the abdominal wall occurred in one Silicone group case and hemorrhage from liver occurred in one Penrose group case. Conclusion: Liver retraction using a silicone disc and needle forceps in laparoscopic gastrectomy is easy and safe, offering a good visual field and a reduced degree of liver dysfunction.

Metastatic recurrence after resection of pancreatic cancer is considered to be an incurable disease, and discoid lupus erythematosus (DLE)-like lesions are known as a side effect of fluorouracil agents. We report a very rare case of metastatic recurrence of pancreatic cancer in a Japanese man with DLE-like lesions in which long-term complete response was achieved through S-1 monotherapy. A 65-year-old man who had undergone distal pancreatectomy with splenectomy for pancreatic body cancer and had received adjuvant gemcitabine developed postoperative para-aortic lymph node recurrence 17 months after surgery. S-1 monotherapy was started. About 2 weeks after starting this treatment, he developed an erythematous rash on the face and scalp. DLE was diagnosed by skin biopsy. The eruptions were aggravated by the administration of S-1 and improved during periods of respite from S-1. Yet as CA19-9 was reduced by almost half 1 month after starting S-1 chemotherapy, S-1 chemotherapy was continued at a reduced dose. CA19-9 decreased to within a normal range within 6 months after starting S-1 chemotherapy, and a reduction in lymph node metastasis was detected through imaging. The patient is still alive without recurrence or metastasis 113 months after surgery. Even in patients with S-1-induced DLE-like lesions, continuation of S-1 is possible if the dose and duration of S-1 are appropriately regulated and medical therapy is administered for the skin lesions. Further investigation into the possible correlation between skin rash and clinical benefit in connection with S-1 is strongly warranted.

目的:高齢者における膵頭十二指腸切除術（PD）の手術成績と術後長期的栄養指標の推移を明らかにすること．対象・方法: 2009年から2014年までに当施設でPDを施行した100例を対象とした．75歳以上20例（高齢者群）と74歳以下80例（非高齢者群）に分け，手術成績ならびに総蛋白（TP），血清アルブミン（Alb），ヘモグロビン，リンパ球数，“小野寺らのprognostic nutritional index”（PNI）の術前・術後の経時的推移を比較した．結果:手術成績に有意差はみられなかった．高齢者群で術後1年目にTPが，術後3カ月目と1年目にAlbが，術後1週間，1年目にPNIが有意に低下していた．術前値と術後1年目との比較では，TP・Alb・リンパ球数・PNIに有意差は認めなった．結語:PD術後において高齢者の手術成績と術後栄養指標の変動は非高齢者とほぼ同等であった．

4107 Background: Borderline resectable pancreatic cancer (BRPC) has a high probability of a positive surgical margin and poor prognosis because the tumor interacts with surrounding arteries or veins. Chemoradiotherapy (CRT) with S-1 has shown favorable activity in locally advanced pancreatic cancer. This study was designed to assess S-1 and concurrent radiotherapy in a neoadjuvant setting to determine whether it increases R0 resection rate for BRPC. Methods: This was a multicenter, single-arm phase II study. Patients with BRPC received S-1 (40 mg/m² BID) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery if they fulfilled any of the following: (1) bilateral impingement of superior mesenteric vein or portal vein; (2) tumor contact with superior mesenteric artery ≤180°; or (3) tumor contact with common hepatic artery or celiac axis ≤180°. Primary endpoint was R0 resection rate in BRPC confirmed by central review. At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and a threshold values for primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible between December 2012 and May 2016. CRT was completed in 50 patients (96%) and was safe, with mostly grade 1 or 2 adverse events. Protocol treatment was withdrawn before surgery in 12 patients because of progressive disease diagnosed by computed tomography, and in one because of treatment refusal. Ten patients received exploratory laparotomy, or palliative/noncurative resection. In the rest of 29, R0 resection was conducted in 27, and R1 and RX in 1 patient each. This gave an R0 resection rate of 52% in all 52 eligible patients. In the 41 cases of BRPC confirmed by central review, R0 was confirmed in 26 (63%). Destruction of > 50% of tumor cells was confirmed pathologically in 10 (32%). Postoperative grade III/IV adverse events according to Clavien–Dindo classification were observed in 6 (15%). Conclusions: S-1 and concurrent radiotherapy were well tolerated and found to be effective in BRPC. A randomized controlled trial comparing neoadjuvant CRT and chemotherapy, including gemcitabine+nab-paclitaxel, for BRPC is under planning. Clinical trial information: NCT02459652.

Purpose It is well known that pancreatic ductal adenocarcinoma (PDAC) is accompanied with pancreatic atrophy and fibrosis. We previously reported the correlation between pancreatic volume and body surface area (BSA) and significant reduction of BSA-adjusted pancreatic volume in pancreatic cancer patients. We evaluated potential correlation between BSA-adjusted pancreatic volume and PDAC prognosis. Methods The study subjects were 48 pancreatic cancer patients received pancreatectomy at our department from June 2006 to September 2012. Pancreatic volumetry was retrospectively performed using the images obtained from multidetector computed tomography (MDCT) before the surgery. BSA-adjusted pancreatic volumes were calculated and analyzed for potential correlation with the prognosis. Results Average BSA-adjusted pancreatic volume among 48 cases was 35.4 ± 11.9 mL/m². Types of surgery included 24 cases with pancreaticoduodenectomy (PD) and 24 cases with distal pancreatectomy (DP). The cases with BSA-adjusted pancreatic volume less than 40 mL/m² had significantly poorer prognosis compared to the cases of 40 mL/m² and greater (3-year survival rate: 32.4% vs 64.3%). Statistical analysis identified four prognosis factors, ie. BSA-adjusted pancreatic volume less than 40 mL/m², postoperative adjuvant chemotherapy, lymph node metastasis and lymphatic invasion. Conclusions This study demonstrated BSA-adjusted pancreatic volume as a prognosis factor for PDAC and the volume of 40 mL/m² is considered to be the cutoff value.