Epidermoid cyst within an intrapancreatic accessory spleen exhibiting abrupt changes in serum carbohydrate antigen 19-9 level: a case report.

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.

Validation and clinical usefulness of pre- and postoperative systemic inflammatory parameters as prognostic markers in patients with potentially resectable pancreatic cancer.

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.

Human equilibrative nucleoside transporter-1 expression is a predictor in patients with resected pancreatic cancer treated with adjuvant S-1 chemotherapy.

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.

Outcomes in patients with pancreatic cancer as a secondary malignancy: a retrospective single-institution study.

PURPOSE: 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). METHODS: We retrospectively reviewed clinical data from 185 PC patients undergoing surgical resection. Patients were divided into the 1st and 2nd primary PC groups. RESULTS: 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 < 0.001) and was more frequently asymptomatic compared to the 1st primary PC group (67.4 vs. 31.0%, respectively, P < 0.001). The tumor size was larger, and extrapancreatic nerve plexus invasion, venous invasion, and lymph node metastasis were more frequently observed in the 1st primary PC group. The rate of adjuvant therapy administration was lower in 2nd primary PC patients (72.5 vs. 51.2%, P = 0.009). In the survival analysis, no significant difference in overall or disease-free survival was found between the two groups (16.8 vs. 16.4 months, P = 0.725, and 8.7 vs. 9.3 months, P = 0.284, respectively). CONCLUSION: Despite significant surveillance bias, such as earlier detection in 2nd primary PC, the outcomes of patients with 2nd primary PC were comparable to those of patients with 1st primary PC. Further investigation with a larger sample size and matching for patient age and tumor stage in both groups is needed to elucidate the biological features of 2nd primary PC.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

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.

Association of Preoperative Platelet-to-Lymphocyte Ratio with Poor Outcome in Patients with Distal Cholangiocarcinoma.

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 lym-phocyte 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.

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review.

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.

Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01).

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 < 0.001). Problems in mobility and pain/discomfort were also less frequent in the S-1 group than in the gemcitabine group in that period. Quality-adjusted life months were longer in the S-1 group than in the gemcitabine group (P < 0.001). 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.

Clinical implications of the proliferative ability of the squamous component regarding tumor progression of adenosquamous carcinoma of the pancreas: A preliminary report.

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.

Adenosquamous carcinoma in the biliary tract: association of the proliferative ability of the squamous component with its proportion and tumor progression.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prognostic significance of intraoperative peritoneal washing cytology for patients with potentially resectable pancreatic ductal adenocarcinoma.

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.

Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01).

BACKGROUND: 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. METHODS: 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). FINDINGS: 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-inferiority<0.0001, p<0.0001 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. INTERPRETATION: 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. FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.

Influence of preoperative anti-cancer therapy on resectability and perioperative outcomes in patients with pancreatic cancer: project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

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.

[A case report of conversion therapy for initially unresectable colorectal cancer liver metastases after cetuximab as third-line treatment].

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.

Whole stomach and spleen preserving total pancreatectomy: a new surgical technique for pancreatic cancer.

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.

Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Stomach-preserving distal pancreatectomy with combined resection of the celiac artery: radical procedure for locally advanced cancer of the pancreatic body.

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.

Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings.

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.

Prophylactic hepatic irradiation following curative resection of pancreatic cancer.

BACKGROUND/PURPOSE: It is unlikely that adjuvant chemoradiotherapy applied to the pancreatic bed alone significantly improves the survival of patients with resectable pancreatic cancer. The aim of the present study was to determine whether prophylactic hepatic irradiation (PHI) improved patient outcome after the curative resection of pancreatic cancer. METHODS: The study population was comprised of 34 patients (PHI group) who were administered PHI after curative resection of pancreatic cancer between September 1994 and December 2003. The whole liver was irradiated with a total dose of 19.8-22.0 Gy under continuous infusion of 5-fluorouracil. The cumulative rate of liver metastasis and the survival outcomes of the PHI group were compared with those of 31 patients without PHI (non-PHI group) who underwent curative resection of pancreatic cancer. RESULTS: The planned PHI was completed for 32 of the 34 patients. Two patients developed complications that might have been PHI-related. One developed liver abscesses which were successfully managed by percutaneous drainage. The other died of liver failure without recurrence 11 months after the operation. The cumulative incidence of liver metastasis was significantly lower for the PHI group than the non-PHI group (P=0.0455). Patients in the PHI group also survived significantly longer compared to those in the non-PHI group (P=0.0002). CONCLUSIONS: The present findings suggest that PHI is well tolerated and is a potentially effective treatment strategy after curative resection of pancreatic cancer, thereby providing the basis for a randomized controlled trial.

A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.