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Background Several preoperative systemic inflammatory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and Glasgow prognostic score, have been reported to be associated with the prognosis of solid tumors. In this study, we compared pre- and postoperative hematological inflammatory parameters and validated their prognostic significance in pancreatic cancer patients who underwent surgical resection. Methods Clinical records from 211 consecutive pancreatic cancer patients who underwent surgical resection at our institution were retrospectively analyzed. The optimal cutoff values of hematological inflammatory parameters, including lymphocyte count, NLR, PLR, LMR, and PNI, were determined by time-dependent receiver-operating characteristic analysis. Results The postoperative neutrophil count and serum albumin level were significantly decreased in patients who underwent pancreatoduodenectomy (PD group) and in those who underwent distal pancreatectomy (DP group) compared to the levels at baseline. The postoperative lymphocyte count, monocyte count, and platelet count were significantly increased in the DP group compared to those at baseline. As a result, the postoperative NLR and PNI significantly decreased in both groups. The multivariate analysis identified intraoperative peritoneal washing cytology, administration of adjuvant therapy, tumor size, extrapancreatic nerve plexus invasion, and preoperative PLR as independent prognostic factors for overall survival. Conclusions Systemic inflammatory responses were altered after pancreatic resection in pancreatic cancer patients. Preoperative PLR may be a useful prognostic marker in pancreatic cancer patients undergoing surgical resection.

Background: Several preoperative systemic inflammatory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and Glasgow Prognostic Score, have been reported to be associated with the prognosis of solid tumors. However, there are conflicting survival data regarding these parameters in cholangiocarcinoma. Objectives: In this study, we performed a retrospective cohort analysis of patients with distal cholangiocarcinoma (DCC) who underwent surgical resection to evaluate the prognostic value of a cluster of preoperative hematological inflammatory parameters for survival. Method: Fifty-three patients with DCC who underwent pancreaticoduodenectomy with curative intent were enrolled. The optimal cutoff values of hematological inflammatory parameters, including the absolute lym­phocyte count, NLR, PLR, and LMR, were determined by time-dependent receiver operating characteristic analysis. ­Results: The univariate analysis for overall survival (OS) of conventional factors and hematological inflammatory parameters identified that portal vein invasion and PLR had p values of ≤0.1. The univariate analysis for disease-free survival (DFS) identified that lymph node metastasis, PLR, lymphocyte count, and number of positive lymph nodes (≥3) had p values of ≤0.1. These factors were incorporated into the full model and variables were selected using the backward stepwise method. The multivariate analysis identified portal vein invasion and high PLR as independent prognostic factors for OS (p = 0.033 and 0.039, respectively) and high PLR and number of positive lymph nodes (≥3) as independent prognostic factors for DFS (p = 0.016 and 0.004, respectively). Conclusions: Preoperative PLR assessment may be useful for detecting high-risk DCC patients undergoing surgical resection for aggressive adjuvant therapy.

Background Epidermoid cyst within an intrapancreatic accessory spleen (ECIAS) is a rare disease. While the detection of solid components relevant to an accessory spleen is a key diagnostic finding, the differential diagnosis between ECIAS and malignant tumors is difficult without resection in patients with no other findings of an accessory spleen. Case presentation A 73-year-old male was found to have an elevated carbohydrate antigen (CA) 19-9 level (95 U/mL) at an annual checkup, and a cystic lesion in the pancreatic tail was located by abdominal ultrasound. Abdominal magnetic resonance imaging (MRI) revealed a multicystic mass, 24 mm in diameter, which exhibited varying intensities on T2-weighted images. There were no findings suggesting solid components on contrast-enhanced computed tomography and magnetic resonance imaging. Re-evaluation of serum CA 19-9 level revealed a rapid increase to 901 U/mL, which declined to 213 U/mL 3 weeks later. Ruling out the lesion’s malignant potential was difficult, and the patient underwent distal pancreatectomy with splenectomy. Histological findings revealed an ECIAS including multiple cysts, with the mucinous component of each cyst exhibiting different stages of biological reaction; one ruptured cyst exhibited inflammatory changes. Conclusions Careful observation for changes in serum CA 19-9 level and MRI findings might facilitate the diagnosis of ECIAS without a solid component by imaging studies.

Objectives The objectives of this study were to examine the clinicopathological characteristics of patients with adenosquamous carcinoma of the pancreas (ASCP) and assess whether the proliferative ability of the squamous cell carcinoma (SCC) component contributes to either its proportion within the tumor or tumor progression. Methods We retrospectively reviewed 12 patients with resected ASCP and compared their clinicopathological characteristics with those of 161 patients with adenocarcinoma of the pancreas (ACP). The Ki-67 indexes of the separate ASCP components were assessed. Results All the clinicopathological characteristics and outcomes were similar between the ASCP patients and ACP patients. Among the 12 ASCP cases, nine exhibited higher Ki-67 levels in the SCC component than in the corresponding adenocarcinoma (AC) component at primary sites (P = 0.022). The component with a higher Ki-67 level coincided with the predominant component at the primary site in nine of 11 patients. In all 10 patients who presented lymph node metastasis, the metastases almost entirely consisted of either the SCC or AC component. The SCC component was absent from metastatic lymph nodes in five of 10 patients even though the Ki-67 levels at the primary site in four of these patients were higher in the SCC component than in the AC component. Conclusions The enhanced proliferative ability of the SCC component of ASCP is reflected by its proportion within the tumor. However, other biological factors might contribute to metastasis in ASCP.

Objective The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. Methods The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (−) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. Results The overall survival (OS) rate was significantly higher in BR-A(−) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(−) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(−) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. Conclusion The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

The high expression of human equilibrative nucleoside transporter‐1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5‐fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S‐1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S‐1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S‐1 arm., In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = .007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm.

This study aimed to evaluate the clinicopathological features and oncological outcomes of pancreatic cancer (PC) patients with prior malignancies (2nd primary PC) compared with those of patients without any prior malignancies in their history (1st primary PC). We retrospectively reviewed clinical data from 185 PC patients undergoing surgical resection. Patients were divided into the 1st and 2nd primary PC groups. Forty-three patients (23.2%) had a history of prior malignancy. The 2nd primary PC group was significantly older than the 1st primary PC group (mean, 72.1 vs. 65.9 years, respectively, P

Aim In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). Patients and methods A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. Results Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the log-rank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. Conclusion Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.

Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival.We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655).385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority0.0001, p0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group.Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients.Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.

Purpose To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m2 under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m2. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m2) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

The current study presents the case of a 72-year-old woman with a rapidly enlarged liver metastasis from esophagogastric junction (EGJ) cancer, accompanied by progressive leukocytosis (47,680/µl) and elevated serum granulocyte colony-stimulating factor (G-CSF; 779 pg/ml). The patient underwent right hemihepatectomy 26 months after a total gastrectomy. On the seventh post-operative day the patient's leukocyte count and serum G-CSF level decreased to 4,280/µl and ≤19.5 pg/ml, respectively. Histologically, the lesion was a well to moderately differentiated adenocarcinoma similar to the primary lesion. Therefore, this tumor was clinically diagnosed as a G-CSF-producing liver metastasis from EGJ cancer, although immunohistochemical staining for G-CSF was negative. A right pulmonary nodule detected simultaneously with the hepatic mass was resected four months following the hepatectomy and was diagnosed as a pulmonary metastasis. The patient's leukocyte count was normal at the time of her initial surgery for EGJ cancer, and her clinical course varied for different metastatic sites. The liver metastasis was accompanied by progressive leukocytosis and elevated serum G-CSF and demonstrated rapid tumor growth during a six-month period, whereas the non-G-CSF-producing pulmonary metastasis grew slowly during the same period. In addition 21 reported cases of G-CSF-producing upper gastrointestinal tract cancer were reviewed to elucidate the clinicopathological features of this disease.

Background Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. Methods Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. Results Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P Conclusion Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. Clinical trial registration number UMIN000000655 at UMIN CTR.

The purpose of this study was to evaluate the association of the proliferative ability of squamous cell carcinoma (SCC) component with its proportion and tumor progression in adenosquamous carcinoma (ASC) in the biliary tract.Nine patients with ASC in the biliary tract (four each in the gallbladder and the extrahepatic bile duct and one in the ampulla of Vater) who underwent surgical resection were retrospectively reviewed.The proportion of the SCC component in the primary sites ranged from 30% to 95%. The Ki-67 index of the SCC component was higher than that of the adenocarcinoma component in all cases, regardless of the component ratio in the patients' primary lesions. Predominance of the SCC component in the advancing region of the tumor, in angiolymphatic invasion and in perineural invasion was observed in most of the cases. The component ratio in metastatic lymph nodes differed from that in the corresponding primary lesions in all six cases with lymph node metastasis. Among these cases, the proportion of the SCC component was increased in the metastatic lymph nodes compared with that in the corresponding primary lesion in two cases, whereas the proportion was decreased in four cases.The SCC component of ASC in the biliary tract displayed a relatively higher proliferative ability, which might be associated with local invasiveness. However, not only the high proliferative ability of the SCC component but also other biological factors might contribute to tumor progression and metastasis in ASC of the biliary tract.

4127 Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis when treated with upfront surgery. This study was designed to assess whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate. 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 the superior mesenteric vein or portal vein; and (2) tumor contact ≤180° with the superior mesenteric artery, common hepatic artery, or celiac axis. The primary endpoint was the R0 resection rate in BRPC confirmed by central review. Secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate (RECISTv1.1), pathological response rate, surgical morbidity (Clavien–Dindo classification), and toxicity (CTCAEv4.0). At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and threshold value for the primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible, of whom 41 had BRPC by central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% (95% CI, 37.6%–66.0%) in 52 eligible patients and 63% (95% CI, 46.9%–77.9%) in 41 patients with BRPC. The radiological response rate was 5.8%, while destruction of > 50% of tumor cells was shown microscopically in 32% of patients. Postoperative grade III/IV adverse events were observed in 7.5% of operated patients. Among the 52 eligible patients, the 2-year OS rate, median OS, and median PFS were 51%, 25.8 mo, and 6.7 mo. Of the 41 patients with BRPC, the 2-year OS rate, median OS, and median PFS were 58%, 30.8 mo, and 10.4 mo. Conclusions: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate with encouraging survival rates in BRPC. A phase II/III trial evaluating this treatment is ongoing. Clinical trial information: NCT02459652.

Background Little is known about the effects of neoadjuvant therapy on outcomes in patients with pancreatic cancer. This study evaluated the effects of neoadjuvant therapy on resectability and perioperative outcomes. Methods A total of 992 patients were enrolled, with 971 deemed eligible. Of these, 582 had resectable tumors and 389 had borderline resectable tumors, and 388 patients received neoadjuvant therapy. Demographic characteristics and peri- and postoperative parameters were assessed by a questionnaire survey. Results The R0 rate was significantly higher in patients with resectable tumors who received neoadjuvant therapy than in those who underwent surgery first, but no significant difference was noted in patients with borderline resectable tumors. Operation time was significantly longer and blood loss was significantly greater in patients who received neoadjuvant therapy than in those who underwent surgery first, but there were no significant differences in specific complications and mortality rates. The node positivity rate was significantly lower in the neoadjuvant than in the surgery-first group, indicating that the former had significantly lower stage tumors. Conclusions Neoadjuvant therapy may not increase the mortality and morbidity rate and may be able to increase the chance for curative resection against resectable tumor.

Background The prognostic significance of intraoperative peritoneal washing cytology (IPWC) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the treatment strategy for PDAC patients with positive cytology has not been established. Objectives The objective of this study was to evaluate the clinical significance of IPWC in PDAC patients. Methods This study included a retrospective cohort of 166 patients with curatively resected PDAC who underwent IPWC. Results Overall, 17 patients (10%) had positive cytology (CY+), and 149 (90%) patients were negative (CY−). Tumor location in the pancreatic body and/or tail and pancreatic anterior capsular invasion were independent predictors of a CY+ status (P = 0.012 and 0.041, respectively). The initial recurrence occurred at the peritoneum with a significantly higher frequency in CY+ patients (50%) than in CY− patients (12%) (P = 0.003). The median overall survival (OS) for CY+ patients was 12 months. The OS rates at 1 and 3 years were significantly higher for CY− patients (75.1% and 35.3%, respectively) versus CY+ patients (47.1% and 17.6%, respectively; P = 0.012). However, one CY+ patient survived for 66 months, and another two CY+ patients have survived for more than three years after surgery without evidence of peritoneal recurrence. In the multivariate analysis, the independent predictors of OS were a CY+ status, lymph node metastasis, and adjuvant chemotherapy. Conclusions This study demonstrates that positive IPWC predicts early peritoneal recurrence and a poor prognosis for PDAC patients. However, a small but not insignificant subset of CY+ patients with PDAC may avoid peritoneal carcinomatosis.

Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

To enhance the resectability of cancer of the pancreatic body, a new surgical technique should be developed. Of 25 patients with cancer of the pancreatic body who underwent distal pancreatectomy with curative intent, seven with cancer invasion around the celiac artery underwent stomach-preserving distal pancreatectomy with combined resection of the celiac artery. This procedure secured arterial blood supply to the whole stomach and liver via the inferior pancreaticoduodenal artery without arterial reconstruction. There was no postoperative mortality. One patient developed transient passage disturbance in the duodenum. Another one developed a minor pancreatic fistula. No patients had serious complications related to ischemia of the stomach or liver. The quality of life of the patients after surgery was well maintained, and planned adjuvant therapy was accomplished. Local recurrence was evident in only two patients. The median survival time of patients who underwent distal pancreatectomy with (n = 7) or without (n = 18) resection of the celiac artery was 19 and 25 months, respectively. The overall survival rate was not significantly different between the two groups (P = 0.5300). The present study suggests that this surgical procedure is a rational approach to locally advanced pancreatic body cancer invading around the celiac artery. In view of the feasibility of this procedure, it can also be adopted for less advanced cancer of the pancreatic body to enhance local control and survival.

The autopsy findings of patients who died of recurrence after curative resection of pancreatic cancer may afford a reliable guide to increase long-term survival after surgery. Recurrence patterns were analyzed for 27 autopsied patients who had undergone potentially curative resection of pancreatic cancer. The pattern of recurrence was classified as follows: (1) local recurrence, (2) hepatic metastasis, (3) peritoneal dissemination, (4) para-aortic lymph node metastasis, and (5) distant metastasis not including hepatic metastasis, peritoneal dissemination, and para-aortic lymph node metastasis. Of the 27 autopsied patients, recurrence was confirmed for 22 of 24 patients, except for three who died of early postoperative complications. Eighteen (75%) of the 24 patients had local recurrence, 12 (50%) had hepatic metastasis, and 11 (46%) had both. For four patients, local recurrence confirmed by autopsy was undetectable by computed tomography, because the recurrent lesions had infiltrated without forming a tumor mass. Peritoneal dissemination, para-aortic lymph node metastasis, and distant metastasis were found for eight (33%), five (21%), and 18 (75%) of the cases, respectively. Twenty patients died of cancer, but local recurrence was judged to be the direct cause of death of only four. Local recurrence frequently occurs, but is rarely a direct cause of death, and most patients died of metastatic disease. Therefore, treatment that focuses on local control cannot improve the survival of patients with resectable pancreatic cancer, and thus, treatment regimens that are effective against systemic metastasis are needed.

Though the outcome of resection for locally invasive pancreatic cancer is still poor, it has gradually improved in Japan, and the 5-year survival is now about 10%. However, the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial. We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design.Patients with pancreatic cancer who met our preoperative criteria for inclusion (pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery, or without distant metastasis) underwent laparotomy. Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group (200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy) without resection. The 2 groups were compared for mean survival, hazard ratio, 1-year survival, quality of life scores, and hematologic and blood chemical data.Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group. There was 1 operative death. The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival (62% vs 32 %, P=.05), mean survival time (17 vs 11 months, P.03), and hazard ratio (0.46, P=.04). There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection.Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.

1986年9月から2000年5月までの胃癌切除例1,388例を対象とし,縫合不全群56例と対照群1,332例に分けて臨床病理学的因子の比較を行った.さらに縫合不全群においては治療経過,ロジスティック回帰分析による重症化の危険因子の検討を行った.縫合不全群と対照群の比較において胃切除術式,進行度,合併切除,術中出血量で有意差が認められた.また縫合不全重症化の危険因子の解析では有意性は認められないものの,併存疾患の存在と術中出血量が多いことの関与が推定された.重症症例では,治療期間の有意な延長と開腹ドレナージなどの侵襲的な治療を必要とした.重症症例における死亡例3例は,いずれも膵液漏を併発し,腹腔内出血を起こした症例であった.胃癌手術後消化管縫合不全の危険因子として胃全摘術,進行症例,合併切除,術中出血多量例が考えられた.

高齢者胃癌治療では,根治性の追求とともに合併症や早期他病死を避けるための侵襲の軽減が求められる.今回われわれは治癒切除術が施行された80歳以上の高齢者胃癌49症例を対象として術後予後因子の検討を行った.手術後5年以内の死亡は原病死6例,他病死10例の計16例であった.原病死例では,癌進行度と胃切除範囲が有意な予後要因であったが,リンパ節郭清度の影響は認められなかった.他病死例においては,進行度と術後合併症の有無が有意であり,術後合併症の発症は術中出血量との相関が認められたが,術前諸因子から術後合併症の発症を予測することは困難と考えられた.以上より,進行度が原病死,他病死の双方に影響を有する一方で,リンパ節郭清度の影響は認められず,術中出血量が術後合併症の発症に影響を与えていることから,高齢者胃癌外科治療では必要最小限の切除が望ましいものと考えられた.

症例は70歳,女性. 2000年11月,腹部膨満感を主訴に近医を受診した,上部消化管内視鏡にて十二指腸下行脚に隆起性病変を認め,精査目的で当センター紹介となった.諸検査施行後,十二指腸副乳頭部に発生したcarcinoidと診断した.画像診断上明らかな転移巣を認めなかったが,最大径20mmを越える腫瘍でmicro metastasisの可能性も考慮し切除術を選択した.病理組織学的検索では,最大径15mm,粘膜下層に限局するcarcinoidであったが,検索したリンパ節14個中6個に転移が確認された.自験例を含め十二指腸副乳頭部に発生したcarcinoidは7例報告されているが,いずれも高い転移率を認め,周囲リンパ節郭清を伴う膵頭十二指腸切除が妥当であると考えられた.

A 56-year-old man with advanced gastric cancer was referred to our hospital. Preoperative abdominal computed tomography revealed numerous enlarged lymph nodes, including the lymph nodes of the paraaortic region. The patient underwent total gastralectomy, splenectomy, left-adrenalectomy and resection of the body and tail of the pancreas by Appleby’s method, along with paraaortic lymph node dissection. Microscopic examination revealed that the tumor was a solid type, poorly differentiated adenocarcinoma, which displayed invasion of the serosal surface. There were apparently many lymph node metastases. We identified 31 cancer-positive paraaortic nodes, while the total number of lymph node metastases was 81. It was not possible to administer sufficient postoperative adjuvant chemotherapy, as the patient experienced postoperative complications, including pancreatic fistula and watery diarrhea. Despite the lack of sufficient chemotherapy, the patient has subsequently remained disease-free for 9 years and 3 months, and continues to visit our hospital as an outpatient. In conclusion, we wish to emphasize the need for a critical application of paraaortic lymph node dissection as one modality of multidisciplinary treatment in patients with advanced gastric cancer in whom paraaortic lymph node metastasis is strongly suspected preoperatively.

Background Following pylorus-preserving pancreatoduodenectomy (PPPD), most surgeons use gastrointestinal reconstruction with an end-to-side duodenojejunostomy placed distally to the pancreatojejunostomy and choledochojejunostomy. In contrast, the authors have consistently used PPPD with the Imanaga reconstruction (PPPD-Imanaga) which consists of end-to-end duodenojejunostomy, end-to-side pancreatojejunostomy and choledochojejunostomy, performed in that order. In this study, the movement of bile and food after PPPD-Imanaga was evaluated to document the functional advantages of this method. Methods Twenty-four patients who had undergone PPPD-Imanaga were subjected to hepatobiliary and gastrointestinal dual scintigraphy. The interval between operation and scintigraphy ranged from 28 days to 67 months. Six of the 24 patients underwent repeated dual scintigraphy for the observation of temporal changes in gastrointestinal function. Results The incidence of biliogastric reflux and bile stasis in the jejunal loop was markedly decreased at times later than 2 months after operation. Delay of gastric emptying and bile evacuation, sometimes accompanied by stasis in the jejunal loop, affected the mixing status of bile and food at 1 h after the beginning of imaging. A majority of the patients, however, had a satisfactory mixing status at 2 h. Conclusion The Imanaga reconstruction appears to be a recommendable procedure following PPPD, in light of the bile and food movement achieved in the gastrointestinal tract.

幽門保存胃切除例(pylorus preserving distal gastrectomy: 以下, PPDG と略記)8例を対象として, 消化管・胆道シンチグラフィーによる術後機能評価を行い, 早期胃癌術前症例および通常の幽門側切除, Billroth-1法吻合症例(以下, B-1と略記)との比較を行った. 胆道シンチグラフィーによる胆汁排泄開始時間はPPDG群, 術前群, B-1群において有意な差異は認められなかった. また胆汁の残胃内逆流は, B-1では40%以上に認められるのに対し, PPDG群では術後6か月, 1年ともに, 術前群と同様に認められなかった. 消化管シンチグラフィーによる食物の胃からの排出は, PPDG群では術後6か月において, 術前群, B-1群と比べて有意な停滞が認められるものの, 術後1年の比較では, B-1群と差が認められず, 幽門機能の経時的な回復が示唆された.

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.

Hepatocellular carcinoma with tumor thrombus in the portal trunk and collateral veins in the hepatoduodenal ligament is usually considered to be unresectable. To resect the tumor, it is necessary to handle the portal trunk and bile duct after the hepatic artery and liver parenchyma have been transected without dissection of the hepatoduodenal ligament. In this way, we were able to perform right lobectomy with removal of the tumor thrombus in the portal trunk, avoiding profuse bleeding due to transection of the collateral veins. Our procedure is associated with certain problems, one being whether the tumor thrombus can be separated from the endothelium of the portal vein, and another being related to the radical extent of this operation. The major issue is the radical nature of this procedure. It is presumed that the collateral veins can be extirpated to achieve a curative operation.

巨大な膵腺房細胞癌の切除後に短期間で肝転移をきたした症例を経験したので報告する. 症例は54歳の女性. 主訴は腹部腫瘤で, 右上腹部には超手挙大, 弾性硬な腫瘤を認めた. 腫瘍マーカーはelastase Iなどが高値を示した. 膵頭部腫瘍と診断し膵頭十二指腸切除術を施行した. 被膜を有する11×8×6cmの腫瘍は組織学的に膵外分泌部に類似しており, 電顕像でzymogen顆粒を認め, 膵腺房細胞癌と確定診断しえた. 術後5か月のCTでは再発の兆候はなかったが, 術後8か月のCTで肝右葉に巨大な転移巣を認めた. 肝転移に対してTAEを施行したが, 術後9か月目に肝不全で死亡した. 剖検では, 直径15cm大の巨大な肝転移に加え, 残膵のほとんどが腫瘍で置換される残膵再発が認められた. 被膜化された膵腺房細胞癌の予後は良好であるとされているが, 自験例のごとく急速な肝転移を示す症例もあることを考慮して治療を行う必要がある.

腹腔内の遊離癌細胞を証明することが大腸癌の腹膜再発の予知因子として有用であるかを知るために, 大腸進行癌188例を対象として術中腹腔細胞診を行い臨床病理学的に検討した.腹膜播種例 (P (+)) の細胞診陽性率は53.3% (8/15例) であった. 腹膜播種のない例 (P (-)) の細胞診陽性率は5.8% (10/173例) であり, 深達度別の陽性率はse, siが15.5% (7/45例), ssが2.6% (3/117例) でmpには陽性例はなかった. 細胞診陽性例の組織型では分化型腺癌が8例, 粘液癌が2例であった. 腹膜再発は細胞診陽性例の40% (4/10例) に認め, 陰性例の1.8% (3/163例) よりも有意に高率であり (p

Twenty-six patients who underwent pyloruspreserving pancreaticoduodenectomy (PPPD) for ductal cancer of the head of the pancreas between 1983 and 1993 were reviewed. Gastrointestinal continuity was restored by the methods of Imanaga (n=21) and Traverso (n=5). Combined resection of the portal vein and/or superior mesenteric vein was performed in 13 patients. Surgical complications occurred in 5 patients, but there were no postoperative deaths. Delayed gastric emptying was observed in 42% of patients. The median survival time for all 26 patients was 13 months. Three patients survived for more than 3 years, and one of them is currently alive without recurrence at 10 years. Differences in survival rates were not apparent between patients who underwent PPPD with and without portal vein resection. Survival rate after PPPD was compared with that after pancreaticoduodenectomy (PD) performed between 1974 and 1992; the difference was not significant. Patients who underwent noncurative PPPD had a significantly better survival rate than those who underwent noncurative PD (P

The pathogenic factors of cholelithiasis after gastrectomy were analyzed using multiple regressoin analysis. Subjects were 136 patients who underwent curative resection of gastric cancer and were followed by ultrasonography for more than 2 years. Of the 136 patients the prevalence of gallstone was found in 22 patients (16.2%): 21 patients had asymptomatic gallstone and one patient symptomatic gallstone who underwent surgery. Factors employed as variables in multiple regression analysis were age, sex of patient, preoperative serum level of total cholesterol and total protein and progression of cancer, extent of gastrectomy: subtotal or total, with or without combined resection of other organ, extent of lymphadenectomy, method of reconstruction, presence or absence of blood infusion, adjuvant chemotherapy and postoperative complications, and the preoperative degree of obesity: body mass index (BMI). Among these factors, only the degree of obesity had a significant correlation with cholelithiasis after gastrectomy. There was a week tendency to have cholelithiasis in patients with some factors including advanced age, sex (male), advanced gastric cancer, extended lymphadenectomy, blood transfusion (+), and postoperative complication (-).

The introduction of monoclonal antibodies into the treatment protocols for metastatic colorectal cancer(mCRC)has significantly improved outcomes. There are some patients with mCRC, initially judged unresectable, who become resectable after chemotherapy. For patients with isolated liver metastases, surgical resection is recommended when feasible. We experienced a case in which an initially unresectable mCRC liver metastases converted into a resectable one after cetuximab monotherapy as third-line treatment. The sample from hepatectomy was a pathologically complete response; no remnants were detected. The management of liver metastases contributes to improvements in the clinical setting. For conducting a multimodal treatment of mCRC, the participation of various specialists such as medical oncologists, colorectal/hepaticsurgeons and diagnostic/therapeutic radiologists is indispensable. Furthermore, it is necessary to construct an evidence-based consensus on potentially resectable CRC liver metastases in each hospital.

To evaluate the effect of the oral fluoropyrimidines, tegafur and uracil (UFT) and 5-fluorouracil (5-FU), a pharmacodynamic analysis was conducted using a nude mouse system and patients. In the nude mouse system, UFT and 5-FU showed similar marginal effects against the human tumor xenograft Co-4, and the concentration of 5-FU in serum 1 h after the last administration being 0.04 micrograms/ml, which was assumed to be the minimum effective concentration. (MEC). Postoperative patients were subdivided into three groups, being: those who underwent subtotal gastrectomy and received UFT; those who underwent subtotal gastrectomy and received 5-FU; and those who underwent total gastrectomy and received UFT. In the UFT groups, the concentration of 5-FU in the portal and peripheral blood showed similar elimination in terms of the peak concentration (Cmax) and the area under the curve (AUC). In the 5-FU groups, the AUC and Cmax were significantly higher in portal blood than peripheral blood. The concentrations in the portal blood of the 5-FU group and in the portal and peripheral blood of the UFT group were significantly higher than the MEC (0.04 micrograms/ml). From these pharmacodynamic data, it was concluded that postoperative chemotherapy with oral fluoropyrimidines can achieve the MEC in portal and peripheral blood.

Alpha-fetoprotein (AFP) 産生胃癌切除例10症例の臨床病理学的因子を検討するとともに, proliferatingcell nuclear antigen (PCNA) の発現の程度から, その腫瘍細胞増殖能を検討した.AFP産生胃癌の頻度は同時期の進行胃癌切除例の6.1%で, 肉眼型では2ないし3型の潰瘍形成型を示し, 胃遠位側に存在するものが多かった.組織型別には乳頭状腺癌, 中分化型管状腺癌, 低分化型腺癌と種々のものがみられたが, 多くが中間型および髄様増殖型であり, 硬性型はなかった.また10例中7例が手術時肝転移を有し, 残り3例中1例も肝転移再発死し, 肝転移との強い相関がみられた.PCNAの発現の程度からみた細胞増殖能では, 他の進行胃癌のものにくらべて, AFP産生胃癌の細胞増殖能は高いことが示唆された.

症例は54歳男性.1990年6月集団検診にて食道の異常を指摘され当院を受診.食道造影で胸部上部食道に20×16×10mm大の隆起性病変を認め, 内視鏡で表面にびらんを伴う表在隆起型食道癌と診断した.腫瘤表面よりの生検では扁平上皮癌が得られた.治療は放射線照射50Gyと5-Fu 1,000mg/m2/dayおよびシスプラチン25mg/m2/dayをともに5日間持続静注による化学療法2コース施行した.治癌効果判定で腫瘍の縮小が認められなかったため1991年3月7日手術を施行した.病理組織学的には隆起性病変は正常食道粘膜に覆われており, 腫瘍は粘膜筋板より発生した平滑筋腫であった.腫瘍の表面上皮には生検材料で見られた癌細胞は認められなかった.平滑筋腫を覆う上皮に一致して癌が併存していたが, 放射線化学療法により癌は消失し, 平滑筋腫のみ残存したものと考える.

Total pancreatectomy has been used to treat both benign and malignant diseases of the pancreas. The procedure of total pancreatectomy for invasive pancreatic cancer usually includes distal gastrectomy and splenectomy to prevent ischemic changes due to decreased blood supply. In this report, it was introduced a new technique of total pancreatectomy for invasive pancreatic cancer preserving both the whole stomach and spleen. The patient was a 61 year old man. Preoperative computed tomography (CT) showed a mass of tumor, measuring 23x18x25mm, located in the pancreatic head. It was tried, initially to perform pylorus-preserving pancreatoduodenectomy (PPPD). Repeated frozen section examination of the pancreatic stumps, however, revealed persistent cancer infiltration to the distal pancreas. Therefore, we altered the planned PPPD to total pancreatectomy preserving the whole stomach and spleen with severing both the splenic artery and vein at their origins. The postoperative course was uneventful. Enhanced CT following surgery showed sufficient blood supply to the whole stomach and spleen without any congestive changes of blood flow. This method is considered safe and useful for patients with both benign and malignant disease of the pancreas.

腹会陰式直腸切断術後の直腸癌局所再発例に対して根治的切除を目的とした仙骨合併骨盤内臓器全摘術を施行し,長期健存中の1例を経験したので報告した.症例は67歳の男性で,1984年6月に某医にて直腸癌に対して直腸切断術を受けたが,約14カ月後に会陰痛が出現し,1986年9,月当センターを受診した.臨床所見および骨盤CT所見から仙骨・骨盤壁に浸潤する直腸癌の局所再発と診断し,1986年11月第3仙椎以下の仙骨と骨盤筋群の合併切除を伴う骨盤内臓器全摘術を施行した.術後,会陰痛は改善し,歩行障害を残すことなく軽快退院した.1991年7,月現在,再発の兆候なく生存中である.仙骨合併骨盤内臓器全摘術が施行された進行した局所再発癌症例の治療成績について文献的考察を行った.本例は内外文献の報告例の中でも最も長期の健存がえられている症例のなかの1例であった.

機能温存を考慮した手術術式として, 腹腔動脈幹周囲に浸潤した膵体部癌に対し, 全胃を温存し以下に述べる血管処理を伴う膵体尾部切除術を2症例に施行した.腹腔動脈を大動脈起始部で切離, 総肝動脈, 左胃動脈はその末梢で切離, 下膵十二指腸動脈を温存することにより肝動脈.右胃および右胃大網動脈の血流を上腸間膜動脈経由で確保し, 全胃を温存しえた.2症例とも非治癒切除で, 術中術後照射を併用した.術後合併症は認めず.症例1は62歳男性.腹膜播種を来したが術後41か月現在生存中.症例2は60歳女性.腹腔動脈切除に加えて門脈合併切除を施行.術後4か月で事故死する.再発の有無は不明.腹腔動脈周囲への浸潤を伴う膵体部癌に対しては, 症例を選び, このような全胃温存術式を行い, 術後の栄養状態を少しでも改善して集学的治療を充実させることが, quality of lifeと予後の向上につながるものと考えている.

骨盤内臓器癌の根治術後に発生した骨盤内の難治性瘻孔・死腔に対して, 筋皮弁を用いた修復術を施行し良好な創治癒が得られたので報告した.症例1 : 62歳, 男.直腸癌.術前照射および直腸切断術後に後部尿道瘻が発生した.尿瘻の閉鎖と骨盤内死腔の充填を目的に, 拡大大殿筋皮弁による再手術を行ったところ, 短期間のうちに尿瘻・死腔の完全閉鎖が認められた.症例2 : 70歳女・子宮頸癌の局所再発術前照射および骨盤内臓器全摘出術を施行後, 死腔炎, 恥骨骨髄炎を併発し死腔閉鎖が遅延した.死腔の充填・閉鎖を目的に拡大大殿筋皮弁を用いた修復術を行った, 骨髄炎の治癒は遷延したものの会陰創の一次的創治癒が得られ, 死腔は速やかに閉鎖された.