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Patients diagnosed with resectable pancreatic ductal adenocarcinoma often experience early recurrence even after upfront R0 resection. This study aimed to define early recurrence and identify preoperative risk factors for early recurrence after upfront pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma of the pancreatic head.This multicenter, retrospective study involved 500 patients who underwent pancreaticoduodenectomy resectable pancreatic ductal adenocarcinoma of the pancreatic head at 10 institutions between 2007 and 2016. Preoperative, intraoperative, and postoperative clinicopathological results were compared between early and non-early recurrence groups. Predictors of early recurrence were determined using statistical analyses.Log-rank tests revealed a significant difference (P.001) between recurrence within 3 to 6 months and 6 to 9 months. Early recurrence was subsequently defined as recurrence within 6 months. Patients were categorized into early recurrence (n = 104) and non-early recurrence groups (n = 389). The median overall survival of the early and non-early recurrence groups was 8.6 months and 42.6 months (P.001), respectively. Preoperatively, high carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion, and diabetes mellitus were identified as independent predictive risk factors for early recurrence according to multivariate analysis. Comparing survival rates among patients with 3, 2, 1, or none of these factors, the median overall survival was 17.6 (n = 90), 21.2 (n = 184), 47 (n = 141), and 61.5 (n = 73) months, respectively.The optimal period that defines the early recurrence for resectable pancreatic ductal adenocarcinoma of the pancreatic head is 6 months. Tumor size ≥20 mm, preoperative carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion of the tumor, and the presence of diabetes mellitus are independently associated with early recurrence.

Highlights • Retroperitoneal schwannomas in the abdominal cavity are rare and pose difficulty in preoperative diagnosis and management. • Imaging modalities are usually not sufficient to conclude a diagnosis. • EUS-FNA is useful to confirm preoperative diagnosis. • In EUS-FNA, diagnosis can be accurate if the tumor size is small and tumor is devoid of intratumoral degenerations., Introduction Schwannomas are tumors that originate from the Schwann cells present in the nerve sheath of peripheral nerves. They are commonly seen in cephalocervical areas. Schwannomas in the abdominal cavity are rare. Here, we discuss a case of retroperitoneal schwannoma lying dorsal to pancreas with critical relations to surrounding vessels. Presentation of case A 74 years old asymptomatic male was found with elevated amylase level on his routine blood examination. MR imaging revealed retroperitoneal mass of size 21*18*24 mm. EUS-FNA confirmed retroperitoneal schwannoma. The patient had co-morbid renal disease and was on hemodialysis. During the latest follow up, the tumor was 41*37*41 mm in size located dorsal to the confluence of right renal vein and inferior vena cava. The tumor was in contact with inferior vena cava, horizontal part of duodenum, right renal artery, right kidney, and adrenal gland. The patient underwent laparotomy and the tumor was extract with intact capsule. There were no post-operative complications. Discussion Pre-operative diagnosis in retroperitoneal schwannomas is challenging because imaging features are usually non-specific, and biopsy is the only diagnostic technique. EUS-FNA, which has low diagnostic accuracy, is useful in pre-operative diagnosis of small tumors devoid of intra-tumoral degeneration. Conclusion Retroperitoneal schwannoma is a rare entity. Preoperative diagnosis and curative resection are technically difficult. Care should be given during preoperative investigations and surgical resection of the tumor. EUS-FNA can be a useful diagnostic tool.

Highlights • Severe acute pancreatitis with necrotizing colonic perforation is refractory and the mortality is high. • Step-up approach for severe acute pancreatitis with infectious walled-off necrosis has been increasingly used. • We performed percutaneous drainage, ileostomy, and video-assisted retroperitoneal debridement (VARD) as a step-up approach. • VARD enable sufficient washing of the abscess and radical debridement of the necrotic tissues under direct view., Introduction Colorectal complications including penetration and perforation in acute pancreatitis often become severe and fatal. Effective drainage is pivotal for successful treatment. We present a case of large retroperitoneal abscess with colonic necrotizing perforation due to severe acute pancreatitis treated with video-assisted retroperitoneal debridement (VARD) in a step-up approach. Presentation of case A 31-year-old man was admitted to a general hospital with a diagnosis of severe acute pancreatitis. Ten days after onset, he was referred to our hospital for more intensive treatment. On day 16, he experienced melena and shock, and embolization of the three straight arteries of the descending colon was performed. On day 30, percutaneous drainage was performed for large retroperitoneal abscess. On day 36, ileostomy was performed because the drained pus from the retroperitoneal abscess became feces-like. On day 58, VARD was performed to treat the refractory retroperitoneal abscesses causing high systemic inflammation due to insufficient drainage. On day 85, fluoroscopic examination showed disappearance of the abscess cavity. He was transferred to the previous hospital on day 89. Discussion Colonic perforation due to severe acute pancreatitis often causes sepsis and fatal condition of patients, and drainage of the retroperitoneal abscesses via laparotomy is thought to be highly invasive and risky. VARD enables radical necrosectomy and drainage less invasively. Conclusions VARD enabled less invasive treatment for patients with large retroperitoneal abscess due to colonic necrotizing perforation in severe pancreatitis.

Highlights • There is anomaly that bile ducts and portal veins of the Spiegel lobe do not run together. • Incidence of bile leakage after hepatic surgery was reported to be 2.6–15.6%. • A number of treatment strategies for excluded bile leakage have been reported. • Surgical treatment for excluded bile leakage is a quick and reliable procedure., Inroduction The treatments of excluded bile duct leakage after hepatectomy are not easy and various strategies have been reported, such as surgery, ethanol or fibrin glue injection, and portal vein embolization. Presentation of case A 72-year-old man with a surgical history of laparoscopic ileocecal resection for diverticular bleeding was diagnosed as having hepatocellular carcinoma. Right hemihepatectomy was performed, and computed tomography examination on postoperative day 9 showed abdominal fluid collection in the right subphrenic space. Percutaneous intra-abdominal fluid drainage was performed and it was diagnosed as bile leakage. After that it was diagnosed as excluded bile leakage from the Spiegel lobe by drip infusion cholangiographic-computed tomography and endoscopic retrograde cholangiography. To improve this clinical condition, we performed the Spiegel lobe excision on postoperative day 48. The postoperative course was uneventful and the patient was discharged. Discussion According to the postoperative examination, it appeared that the bile duct from the Spiegel lobe joined to the right main bile duct or the bile duct of the right posterior section. This bile duct anomaly was not detected preoperatively on imaging examination. It is most likely that the bile duct from the Spiegel lobe was cut when the hepatoduodenal ligament in the hepatic hilum was peeled. To prevent excluded bile leakage, the hepatoduodenal ligament should be carefully peeled and ligated instead of using energy devices. Conclusion We consider that surgical treatment for postoperative excluded bile leakage is both a quick and reliable procedure in patients with acceptable liver function and anatomical subject.

Purpose Many patients with advanced cancer choose palliative chemotherapy. Considering its purpose of palliation and not treatment, it is important to consider the life of family caregivers. Family caregivers who experience bereavement undergo extreme stress, which is particularly high among patients’ spouses. The present study aims to clarify the experiences of the spouses of patients at the hospitals in Japan after the notification of palliative chemotherapy discontinuation until bereavement. Method We interviewed the spouses of 13 patients who received palliative chemotherapy using a semistructured interview guide. Each spouse was interviewed twice. The interviews were transcribed verbatim, and key concepts were identified using a grounded theory analytic approach. Results After the hospital's recommendation for palliative chemotherapy discontinuation, the spouses had “bewilderment over having to discontinue palliative chemotherapy” and experienced “difficulty in facing bereavement.” The spouses having “difficulty to give up hope for the patient's survival,” felt “bafflement over caregiving at the terminal stage,” which would be their responsibility in the future. Further, they had “hesitation in being honest to the patient” and were engaged in “knowing how to live with the patient until bereavement.“ Conclusion Nurses need to encourage the patients and spouses to honestly express how they feel from the early stages of palliative chemotherapy. Furthermore, nurses should help spouses with how they face bereavement. This result may help prevent anticipatory grief, which may lead to excessive stress and emotional distress on the family caregivers.

An association between inflammatory/immunonutritional status and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the utility of inflammatory/immunonutritional factors as therapeutic predictors for patients with locally advanced pancreatic cancer treated with chemoradiotherapy (CRT).Ninety-six patients with histologically proven locally advanced pancreatic adenocarcinoma who underwent CRT were enrolled in this study. We evaluated significance of inflammation-based factors as predictors of therapeutic effect and prognosis.The median progression free survival (PFS) and overall survival (OS) of all patients was 10 and 18 months, respectively. A Glasgow prognostic score (GPS) of 2 and plasma fibrinogen levels ≥ 400 mg/dL were independent predictors of poor PFS and OS. A prognostic nutritional index (PNI) ≥ 45 was a predictor of a significantly better reduction rate of the primary tumor. The prognosis between patients with GPS 0/1 and fibrinogen400 mg/dL, GPS 2 or fibrinogen ≥400 mg/dL, and GPS 2 and fibrinogen ≥400 mg/dL were significantly different. Patients with GPS 2 and/or plasma fibrinogen ≥ 400 mg/dL had significantly higher incidence of metastasis within 6 months after CRT.GPS, fibrinogen, PNI are useful therapeutic and prognostic predictors in patients with locally advanced pancreatic cancer treated with CRT.

Introduction Therapeutic strategies for pancreatic trauma vary greatly depending on its severity. Surgical intervention is recommended in cases of severe pancreatic injuries for which standard therapy is not advised. We present a two-step treatment method for severe pancreatic injury using an endoscopic ultrasound (EUS)-guided transgastric internal stent. Clinical case A 50 year-old male with blunt abdominal trauma sustained in a traffic accident was transported with vital signs indicating shock and CT findings of complete transection of the proximal pancreas and a huge haematoma. A life-saving primary emergency damage control operation was performed. A secondary EUS-guided transgastric internal stent was placed into the pancreatic fluid collection on post-operative day 8 (POD 8). The pancreatic juice secreted from the transected pancreatic tail eventually flowed along the internal stent and emptied completely into the stomach. The patient did not display prognostic symptoms at discharge. Discussion EUS-guided transgastric internal stenting is currently considered the first line of therapy for pancreatic pseudocysts. It is recommended that pseudocyst drainage occur at least four weeks or more after its formation. In this severe case of blunt pancreatic trauma, the primary damage control operation saved the patient's life. Following primary surgery, a secondary early operation involved insertion of an EUS-guided transgastric internal stent into the collection of pancreatic juice secreted from the transected pancreatic tail, which allowed complete recovery without surgical extraction or reconstruction of the pancreatic tail. Conclusion In cases of severe pancreatic trauma, practitioners should consider the value of early EUS-guided transgastric internal stenting.

Background Significance and timing of drain removal after pancreatic surgery remain unclear. The aim of this study was to identify optimal indicators to predict severe intra-abdominal complications and determine the appropriate timing of prophylactic drain removal after pancreatoduodenectomy. Materials and methods This study included 151 consecutive patients who underwent pancreatoduodenectomy. We investigated associations between postoperative intra-abdominal complications, drain amylase levels, and duration of postoperative inflammatory response. Results Patients who developed severe intra-abdominal complications showed re-elevation of drain amylase levels after postoperative d 3 and prolonged postoperative inflammatory response, which were most pronounced in patients with severe pancreatic fistula and intra-abdominal abscess, respectively. In contrast, patients with a steady decline in drain amylase levels and short-term postoperative inflammatory response did not develop severe complications, and safe drain removal was possible even when the drain amylase value was more than three times the upper limit of normal serum amylase. Conclusion A combination of trends in the drain amylase level and duration of the inflammatory response in the postoperative period may be optimal indicators for early detection of severe intra-abdominal complications and appropriate timing of drain removal.

Background The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer. Materials and Methods Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40. Results High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P = 0.0094). Significantly increased LVD (P = 0.0175) and a poor prognosis (P = 0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages. Conclusions M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis.

Background: Several tumor-suppressor genes, such as 53-kDa protein (p53), are inactivated in some pancreatic cancers. The lack of a functional p53 has been proposed to be a component of resistance to chemotherapy, resulting in the inhibition of apoptosis. Therefore, reintroduction of wild-type p53 is a commonly used gene therapy strategy for the treatment of various types of cancer, including pancreatic cancer. Objective: The aim of this study was to examine the ability of the histone deacetylase inhibitor, sodium butyrate (NaB), to modulate the expression of p53. Methods: Five human pancreatic carcinoma cell lines (SW-1990, BxPC-3, PANC-1, MIA PaCa-2, JHP-1) were utilized. Two of the cell lines (SW-1990 and JHP-1) lacked p53 expression, as determined by Western blot analysis, and were investigated further. Expression of p53 was determined by densitometry of all bands present in the Western blot. Drug sensitivity was measured with a tetrazolium-based assay by exposing the cells to graded concentrations of NaB and/or anticancer drugs (cisplatin, fluorouracil, SN-38, and paclitaxel). Apoptosis was observed using gel electrophoresis. Results: In the SW-1990 and JHP-1 cell lines, use of 1 mM NaB was found to induce histone acetylation and p53 expression compared with those not treated with NaB (P = 0.01 and P = 0.018, respectively). Sensitivity to cisplatin (P = 0.021), fluorouracil (P = 0.046), and SN-38 (P = 0.039) was significantly enhanced by NaB treatment compared with nontreatment. However, sensitivity to paclitaxel was not significantly different between untreated and NaB-treated cells. A higher frequency of apoptosis was observed in NaB-treated cells compared with that of control cells. Conclusion: This in vitro study found that NaB induced p53 expression in 2 pancreatic cancer cell lines (SW-1990 and JHP-1). Moreover, NaB acted on a biochemical modulator for antieuplastic therapy. Future research is necessary to assess the value of these findings.

Lymphatic dissemination is one of the most important metastatic routes for pancreatic cancer. According to previous reports, the presence of histologically positive nodal metastases is an important prognostic factor in patients with pancreatic cancer. However, outcome of patients, even those without nodal metastases, who underwent a histologically curative operation for pancreatic cancer is significantly worse than expected, indicating that the presence of immunohistochemically positive nodal micrometastases is an unfavorable prognostic factor in these patients.

Pancreatic anastomotic leak (leak) remains a persistent problem after pancreaticoduodenectomy (PD). Recent reports indicate a mean occurrence of 10% with a range of 2%-28% of patients. However, valid comparisons for these studies cannot be made because the definition of leak is variable, and many patients deemed to have a leak are not sick. The aim of this study was to determine the meaning of the volume and amylase content of the effluent from surgical drains by comparing these values to actual clinical outcomes. From January 1996 to July 2002, 207 consecutive patients underwent PD. We considered a leak to be present if greater than 30 ml/day of drainage was observed from drains and if that drainage contained an amylase-rich fluid (greater than 5X serum) on or after postoperative day (POD) 5. Cases were then divided into three groups-no leak, chemical leak only (leak but asymptomatic), and a clinical leak group (leak that required therapeutic intervention, reoperation, readmission, or prolonged length of stay). Then the drainage volume and its amylase concentration for every postoperative day were compared between the three groups. There were no operative or hospital deaths, and the mean length of stay (LOS) was 11.2 +/- 6.1 days. Prolonged LOS was set at greater than 17 days (one standard deviation beyond the mean LOS for all cases). Leak was observed in 14% of cases (n = 29) and the patients were subsequently divided into these groups: no leak (n = 178), chemical leak only (n = 12), and clinical leak (n = 17). Surprisingly, the daily drain amylase values did not differ between the chemical leak group and the clinical leak group. The daily volume of drainage on POD 5-8 for the clinical leak group was significantly greater than the volumes of the other two groups, so that a combination of greater than 200 ml/day of drainage on POD 5 with an amylase greater than 5X serum had a positive predictive value (PPV) of 84% and a negative predictive value (NPV) of 99% for a clinically relevant leak. We used broad criteria from drainage effluent to include as many potential leaks as possible. This broad definition of leak selected 14% of the PD patients as having a leak; within this group, all of the clinical complications of leak occurred. By increasing the volume criteria from greater than 30 ml per day to greater than 200 ml per day, the PPV was increased from 59% to 84% while keeping NPV at 99%. Drain data based on the volume and amylase criteria of this study may be useful for early detection of a leak that will have clinical impact. This study's criteria for leak may be a good definition to design a clinical trial.

Background Multiple publications have suggested that outcomes after complex operations are better at high-volume centers. However, of all the potential “outcomes” to measure, only mortality has been studied extensively. The broadest difference in mortality between low- and high-volume centers has been measured after esophagectomy (EG) and pancreaticoduodenectomy (PD). If a low-volume center recorded high mortality, then a broader set of outcomes beyond mortality would be useful for self-assessment. Methods Two single-surgeon prospective databases for outcomes of EG and PD were reviewed in a multispecialty clinic within a tertiary-referral, resident-training hospital. Between January 1996 and December 2002, 174 consecutive patients underwent EG performed by 1 surgeon (25 cases/y), and 232 consecutive patients underwent PD performed by another surgeon (34 cases/y). We measured hospital and 30-day mortality rate, mean operation time (OR time), mean estimated intraoperative blood loss (EBL), mean length of stay (LOS), and the anastomotic leak rate. These outcomes were compared with those of recently published cases for EG and PD. Results Mortality for both operations was zero. After EG, OR time was 394 minutes (literature = 336), EBL was 204 mL (literature = 964), transfusion rate was 3.5% (literature = 34%), LOS was 11.1 days (literature = 16.6), leak was 2.9% (literature = 9.1%), and reoperation was 1.7% (literature = not stated). After PD, OR time was 450 minutes (literature = 431), EBL was 382 mL (literature = 1,183), transfusion rate was 7.3% (literature = not stated), LOS was 11.2 days (literature = 17.8), leak was 6.5% (literature = 9.9%), and reoperation was 0.4% (literature = 3.8%). Conclusions These 2 single-surgeon series provide benchmarks to help better define acceptable outcomes after EG and PD. This assessment demonstrated lower mortality and LOS in a high-volume surgical practice. These outcomes are not associated with OR time but with lower EBL, less need for transfusion, and lower need for reoperation. Anastomotic leaks occurred in both series; however, this was not associated with mortality because of early recognition and the use of nonsurgical minimally invasive techniques. If mortality is high at a low-volume center, then the additional benchmarks of this study, in addition to mortality and LOS, could be used to lower mortality through self-assessment by identifying specific outcomes that need improvement.

The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer.Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups.The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months.EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.

Background: Whether long-term survival and type of recurrence in periampullary cancer are influenced by the type of surgical procedure or not is still obscure. The purpose of this review was to analyze the results at a single institution. Methods: Between 1982 and 1996, 113 consecutive patients with either distal bile duct or ampullary cancers underwent either pylorus-preserving pancreaticoduodenectomy (PPPD) or the Whipple procedure. The median follow-up was 30 months (range 12 to 150). Patient records were reviewed to determine type of recurrence and survival. Results: In distal bile duct or ampullary cancers, comparison of actuarial survival curves between PPPD and the Whipple operation revealed no significant differences. Even in node-positive patients, the 5-year survival rates did not differ significantly between those undergoing PPPD or the Whipple operation. Tumor recurrence was not correlated with the operative method, although among types of tumor recurrence, the rate of blood-borne metastasis was higher in distal bile duct or ampullary cancers. Conclusions: PPPD is an acceptable alternative to the Whipple procedure in the treatment of periampullary cancer. Long-term survival and type of recurrence were not influenced by these types of surgical procedures.