堀口 明彦

This study aimed to validate the DFS (direct fast scarlet) staining in the diagnosis of EC (eosinophilic colitis). The study included 50 patients with EC and 60 with control colons. Among the 60 control samples, 39 and 21 were collected from the ascending and descending colons, respectively. We compared the median number of eosinophils and frequency of eosinophil degranulation by HE (hematoxylin and eosin) and DFS staining between the EC and control groups. In the right hemi-colon, eosinophil count by HE was useful in distinguishing between EC and control (41.5 vs. 26.0 cells/HPF, p < 0.001), but the ideal cutoff value is 27.5 cells/HPF (high-power field). However, this method is not useful in the left hemi-colon (12.5 vs. 13.0 cells/HPF, p = 0.990). The presence of degranulation by DFS allows us to distinguish between the groups even in the left hemi-colon (58% vs. 5%, p < 0.001). DFS staining also enabled a more accurate determination of degranulation than HE. According to the current standard to diagnose EC (count by HE staining ≥20 cells/HPF), mucosal sampling from left hemi-colon is problematic since the number of eosinophils could not be increased even in EC. Determination of degranulated eosinophils by DFS may potentiate the diagnostic performance even in such conditions.

BACKGROUND: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. METHODS: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. RESULTS: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). CONCLUSION: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

OBJECTIVE: This study was performed to demonstrate the clinical application of duodenum-preserving pancreatic head resection (DPPHR) as a surgical treatment for pancreatic neuroendocrine tumors (PNETs) in terms of both curability and maintenance of postoperative quality of life. METHODS: Seven patients diagnosed with PNETs underwent DPPHR from January 2011 to December 2021 at our institution. We investigated the clinical relevance of DPPHR based on the patients' clinicopathological findings. RESULTS: The median operative time was 492 min, and the median blood loss was 302 g. Postoperative complications were evaluated according to the Clavien-Dindo classification, and postoperative intra-abdominal bleeding was observed in one patient. Pathological examination revealed a World Health Organization classification of G1 in six patients and G2 in one patient. Microvascular invasion was observed in two patients (29%); however, no patients developed lymph node metastasis or recurrence during the follow-up period. A daughter lesion was observed near the primary tumor in one patient. All patients achieved curative resection, and no tumor specimens showed positive margins. CONCLUSIONS: DPPHR facilitates anatomical resection of the pancreatic head in patients with PNETs as well as detailed pathological evaluation of the resected specimen. Therefore, this surgical procedure is an acceptable alternative to pancreaticoduodenectomy or enucleation for patients with PNETs.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

PURPOSE: To describe the real-world treatment patterns of systemic therapies for biliary tract cancer (BTC) and to examine the frequency and management of biliary infection in Japan. METHODS: Patients diagnosed with BTC and prescribed systemic therapy between January 2011 and September 2020 were retrieved from the Japanese Medical Data Vision database. The look-back period was set to 5 years. Patient characteristics, treatment patterns, and biliary infection-induced treatment interruption were analyzed. RESULTS: The full analysis set comprised 22 742 patients with a mean age of 71.0 years and 61.6% were male. The most common BTC type was extrahepatic cholangiocarcinoma (44.6%). The three most common first-line regimens were S-1 monotherapy (33.0%), gemcitabine+cisplatin (32.5%), and gemcitabine monotherapy (18.7%) over the entire observation period (January 2011-September 2021). Patients who received monotherapies tended to be older. Biliary infection-induced treatment interruption occurred in 29.5% of patients, with a median time to onset of 64.0 (interquartile range 29.0-145.0) days. The median duration of intravenous antibiotics was 12.0 (interquartile range 4.0-92.0) days. CONCLUSIONS: These results demonstrated potential challenges of BTC in Japanese clinical practice particularly use of multiple regimens, commonly monotherapies, which are not recommended as first-line treatment, and the management of biliary infections during systemic therapy.

症例は68歳男で、19年前に膵体部IPMNに対して膵中央切除+膵管-膵管吻合(Martin手術)を施行された。今回、心窩部痛を主訴に受診し、CTで膵管吻合部から尾側に乏血性腫瘤を認め、残膵癌が疑われた。諸検査の結果から、膵管吻合部に発生したDe novo膵癌が強く疑われたため、残膵切除術を行うこととした。膵切離を行い迅速病理に提出したところ腺癌陽性と診断されたため術式を膵全摘に変更し、術後経過は良好であった。

BACKGROUND: This study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery. METHODS: A total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups. RESULTS: The use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle. CONCLUSION: These results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.

55歳の女性.検診で膵尾部の腫瘍を指摘され,腹腔鏡下膵体尾部切除術が施行された.病理検査の結果,PanNET G3(Ki-67指数>20%)と診断された.術後7ヵ月で胆管拡張と肝機能異常(AST:171U/l,ALT:86U/l)を認めた.腹部造影CTで主膵管内から十二指腸乳頭に充満する腫瘍を認め,上部消化管内視鏡検査では,Vater乳頭から赤色で白苔を有する乳頭状腫瘍の露出を認めたため,残膵全摘出術を施行した.免疫染色ではsynaptophysin,chromogranin Aが陽性で,Ki-67指数は30～40%であり,PanNET G3の再発と診断された.患者は2回目手術から24ヵ月無再発生存中である.(著者抄録)

In this review article, we focus on recent papers on organ-preserving pancreatectomy procedures published since 2010. When comparing central pancreatectomy (CP) and distal pancreatectomy (DP), most studies have concluded that the CP group exhibited significantly lower incidence of new-onset diabetes or diabetes exacerbation than the DP group postoperatively. However, because of increased incidence of morbidities such as pancreatic fistula, the surgeon faces a considerable trade-off between increased short-term morbidity and long-term preservation of endocrine function. When the outcomes of two types of spleen-preserving DP (Kimura and Warshaw procedures) are compared, most studies mentioned the low incidence of postoperative gastric varices and splenic infarction with the Kimura procedure. Although there are several reports regarding the effect of spleen preservation on prevention of postoperative infections, no report on the contribution of spleen preservation to the prevention of overwhelming post-splenectomy infection is seen. The advantages of duodenum-preserving pancreatic head resection (DPPHR) concerning endocrine and exocrine functions continue to be subjects of discussion, mainly due to the limited number of institutions that have adopted this approach; however, DPPHR should be presented as an option for patients due to its low incidence of postoperative cholangitis. Organ-preserving pancreatectomy requires meticulous surgical techniques, and postoperative complications may increase with this surgery compared with standard pancreatectomy, which may be influenced by the surgeon's skill and the surgical facility where the procedure is performed. Nonetheless, this technique has significant long-term advantages in terms of endocrine and exocrine functions and its wider adoption in the future is expected.

Purpose: The present study aimed to determine whether concomitant extrahepatic bile duct resection (EHBDR) improves the prognosis of patients with T2 gallbladder cancer (GBC). Methods: Between 2014 and 2018, 4947 patients with GBC were registered in the National Biliary Tract Cancer Registry in Japan. This included 3804 patients (76.9%) who underwent curative-intent surgical resection; 1609 of these patients had pT2 GBC with no distant metastasis. Of the 1609 patients with GBC, 520 underwent EHBDR and 1089 did not. We compared the patients' backgrounds and disease-specific survival rates between the groups. Results: The frequency of lymph node metastasis was significantly higher in the EHBDR group than in the non-EHBDR group (38.2% vs. 20.7%, p <.001). In the entire cohort, however, there was no significant difference in disease-specific survival between the two groups (76% vs. 79%, p =.410). The EHBDR group had a significantly higher incidence of postoperative complications (Clavien–Dindo classification grade = 3) (32.4% vs. 11.7%, p <.001). When we focused on the survival of only T2N1 patients who underwent gallbladder bed resection, the prognosis was significantly improved for the EHBDR group (5-year survival rate: 64% vs. 54%, p =.017). The non-EHBDR group was subcategorized into two groups: D2 dissection and D1 dissection or sampling, and survival curves were compared between these subgroups. Although the EHBDR group tended to have a favorable prognosis compared to the D2 group, this difference was not significant (p =.167). However, the EHBDR group had a significantly greater prognosis than the D1 dissection or sampling group (5 year-survival rate: 64 vs. 49%, p =.027). Conclusions: The EHBDR may improve the prognosis of patients with T2 gall bladder cancer with lymph node metastases; however, its indication should be carefully determined because of the increased risk of postoperative complications.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.

局所進行切除不能膵癌に対してFOLFIRINOX+放射線療法を行った後,conversion surgeryを施行した1例について報告する。症例は70歳代,女性。食後の腹痛を主訴に近医を受診し,腹部造影CTを撮影したところ,膵鉤部に上腸間膜動脈,第1空腸動脈,第2空腸動脈浸潤(>180°)を伴う不整形腫瘤を認めた。画像上,UR-LA(sm),cT4N0M0,cStage IIIの膵癌と診断され,mFOLFIRINOX 5コース施行した。その後,局所制御を目的として,放射線療法50.4Gy(三次元原体照射)を追加した。CA19-9は394.1U/mLから10.5U/mLへ低下した。治療効果はRECIST:partial responseと判定した。この後,根治術可能と判断し,初回治療から8ヵ月後に亜全胃温存膵頭十二指腸切除術を施行した。腫瘍は3×2mm相当とごくわずかな範囲に認められ,pStage IA,R0,術前化学療法の治療効果判定はEvans Grade IIIであった。患者は術後5ヵ月無再発生存中である。(著者抄録)

S状結腸癌および多発肝転移に対して化学療法後,肝切除術を施行し病理結果で完全寛解を得たが,化学療法中止後肝局所再発を来したため再肝切除を行った1例を報告する。下腹部痛で当院救急外来を受診した。大腸内視鏡では全周性のII型腫瘍を認め生検にて高分化型腺癌と診断された。根治目的にて腹腔鏡下S状結腸切除+D3リンパ節郭清を施行した。術後CTにてS5,S7,S8に肝転移を認め,Bev+modified FOLFOX(mFOLFOX)を11サイクル施行した。肝転移はいずれの部位でも縮小し肝右葉切除術を施行した。切除標本からはviableな癌組織は認めず完全寛解と考えられた。術後Bev+mFOLFOXを6サイクル再開し寛解を維持していたが,化学療法を中止した3ヵ月後,肝切除後1年6ヵ月後のフォローアップCTにて肝断端の局所再発を認め,肝転移局所再発と診断し開腹肝部分切除を行った。患者は術後9ヵ月現在,無再発生存中でありmFOLFOXを再開している。(著者抄録)