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BACKGROUND/PURPOSE Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. METHODS We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels ("strong", "medium", "weak", "very weak"). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. RESULTS These guidelines address 3 subjects: diagnostic, chemotherapeutic, and surgical approaches. They include 9 clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one "column". CONCLUSIONS This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

BACKGROUND We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC. METHODS Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020. RESULTS Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P

Aim Right‐half dissection of the superior mesenteric artery (SMA) nerve plexus in pancreatoduodenectomy for pancreatic cancer was initiated to accomplish R0 resection; however, subsequent refractory diarrhea was a major concern. This study aimed to evaluate the necessity of this technique. Methods From April 2014 to June 2018, 74 patients with pancreatic head cancer were randomly allocated to either Group A, in which right‐half dissection of the SMA nerve plexus was performed (n = 37), or Group B, in which total preservation of the nerve plexus was performed (n = 37). Short‐term, long‐term, and survival outcomes were prospectively compared between the groups. Results The patient demographics, including the R0 resection rate, were not significantly different between the groups. Postoperative diarrhea occurred in 26 (70.3%) patients in Group A and 18 (48.6%) patients in Group B. There was a tendency for the development of severe diarrhea in Group A within 1 year postoperatively, and the frequency of diarrhea gradually decreased within 2 years, although that did not affect tolerance to adjuvant chemotherapy. There was no difference in either locoregional recurrence (27.0% vs 32.4%) or systemic recurrence (46.0% vs 46.0%). The median overall survival time in Groups A and B was 37.9 and 34.6 months, respectively (P = 0.77). Conclusion We did not demonstrate a clinical impact of right‐half dissection of the SMA nerve plexus on locoregional recurrence or survival. Therefore, the prophylactic dissection of the SMA nerve plexus is unnecessary given that refractory diarrhea could be induced by this technique (UMIN000012241)., The necessity of right‐half dissection of the SMA nerve plexus in pancreatoduodenectomy for pancreatic cancer was evaluated. We did not demonstrate the clinical impact of this technique on locoregional recurrence or survival. Therefore, the prophylactic dissection is unnecessary, given that refractory diarrhea could be induced by this technique.

Background/Purpose We examined therapeutic strategies for pancreatic neuroendocrine neoplasm (pNEN) associated with MEN1 (M‐pNEN) by investigating clinicopathological features and menin expression. Methods Seventy‐seven patients who underwent resection of pNEN at our department from January 2001 to December 2017 were retrospectively analyzed. Immunohistochemical analysis of menin was performed using resected specimens. Results Seven patients (9%) met the diagnostic criteria for MEN1. M‐pNEN had more tumors (P, This study aimed to describe therapeutic strategies for pancreatic neuroendocrine neoplasm associated with multiple endocrine neoplasia type 1 (M‐pNEN) by investigating the clinicopathological features and menin expression. Sonoda and colleagues concluded that minimal resection with strict follow‐up is recommended rather than extensive pancreatic resections for consideration of recurrence in M‐pNEN.

Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2. The enzyme 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15‐PGDH suppression are unclear. The current study was carried out to elucidate the molecular mechanisms and clinical significance of 15‐PGDH suppression in PDAC. Here, we showed that interleukin‐1β (IL‐1β), a pro‐inflammatory cytokine, downregulates 15‐PGDH expression in PDAC cells, and that IL‐1β expression was inversely correlated with 15‐PGDH levels in frozen PDAC tissues. We also found that activated macrophages produced IL‐1β and reduced 15‐PGDH expression in PDAC cells. Furthermore, the number of CD163‐positive tumor‐associated macrophages was shown to be inversely correlated with 15‐PGDH levels in PDAC cells by immunohistochemical staining of 107 PDAC samples. Finally, we found that low 15‐PGDH expression was significantly associated with advanced tumors, presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC patients. Our results indicate that IL‐1β derived from TAMs suppresses 15‐PGDH expression in PDAC cells, resulting in poor prognosis of PDAC patients.

Aim Postoperative recurrence beyond the Milan criteria is one of poor prognostic factors for hepatocellular carcinoma patients treated with various treatments. We investigated the most useful inflammation-based prognostic score for predicting recurrences beyond the Milan criteria after initial liver resection. Methods From January 2007 to December 2012, 271 consecutive patients with hepatocellular carcinoma undergoing curative liver resection were enrolled. Patients were divided according to the initial recurrence pattern; the recurrence beyond the Milan criteria and the others (recurrence within the Milan criteria and no recurrence). The patients were classified into two groups: low-platelet-to-lymphocyte ratio (PLR) (

Preoperatively evaluating the resectability of pancreatobiliary cancers is difficult. The aim of this study was to investigate the benefit of staging laparoscopy in unresectable pancreatobiliary cancers. Between 2010 and 2013, 25 patients with pancreatobiliary cancers underwent staging laparoscopy after conventional tumor staging; they were compared with 10 patients who had unresectable or metastatic tumors that were found during laparotomy. Staging laparoscopy did not show unresectable factors in 11 patients, and resections were performed in these patients. Unresectable factors were found in other 14 patients who underwent staging laparoscopy. In these patients, chemotherapy was started after median postoperative day 3 (range, 2–10 days). This period was significantly longer in patients who received unnecessary laparotomy; chemotherapy was started after median postoperative day 11 (range, 6–15 days). These results suggest that staging laparoscopy, while avoiding laparotomy with unsuccessful resection, can lead to rapid induction of chemotherapy for unresectable pancreatobiliary cancers.

AIM The prognostic value of lymphocyte infiltration into hepatocellular carcinoma (HCC) is still controversial, and it has not been reported in hepatitis B virus (HBV)-positive or non-B non-C (NBNC) HCC. The aim of this study is to assess the prognostic significance of lymphocyte infiltrate in tumor for HBV-positive and NBNC HCC patients. METHODS This study investigated 145 HBV-positive or NBNC patients who underwent hepatectomy for HCC between January 2001 and May 2009. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to lymphocyte infiltration in tumor. RESULTS In patients with low lymphocyte infiltration, the 5-year recurrence rate was higher and OS was poor (86.4 and 44.1%, respectively) than that of the patients with high lymphocyte infiltration (55.3 and 83.7%, respectively). Multivariate analyses revealed that independent risk factors for recurrence were low albumin value (hazard ratio [HR] 2.33, P = 0.009), high American Joint Committee on Cancer (AJCC) T stage (HR 2.31, P

Metachronous rectal liver metastasis (15 mm in segment 8 ventral) was managed with laparoscopic hepatectomy using segmental blood flow occlusion with radiofrequency ablation. During liver dissection, the ischemic area was visible as a distinct hypoechoic area on intraoperative enhanced ultrasound; with a photodynamic eye camera, it appeared as a discolored lesion. The resection was completed with adequate margins.

The aim of this study was to assess the effects of postoperative body weight loss on long-term survival after resection for pancreatic cancer.A total of 93 patients with primary pancreatic cancer underwent pancreatic resection between April 2005 and December 2011. Patient characteristics, preoperative body mass index, and changes in postoperative body weight were evaluated retrospectively and correlated with long-term survival.There was no significant association between survival and preoperative body mass index. Body weight fell by 8.4% at 2 months after surgery and by 9.0% at 4 months after surgery. Severe postoperative body weight losses, both at 2 months (P = .033) and 4 months (P = .014) after surgery, were significantly associated with poor prognosis, especially among patients with stage IA-IIA pancreatic cancer (n = 43) (P = .005 at 2 months and P.001 at 4 months). Additionally, severe body weight loss tended to be associated with shorter survival among patients with stage IIB-III pancreatic cancer (n = 50), although the difference was not significant. Multivariate analysis revealed that postoperative body weight loss was an independent prognostic factor.The results of this study demonstrated that pancreatic cancer patients with severe postoperative body weight loss have poorer postoperative outcomes.

Aim Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP percentage and protein induced by vitamin K absence/antagonist-II were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early stage HCC within the Milan criteria. Methods This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers. Results In patients with triple positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be hepatitis C virus antibody positivity, non-initial treatment for HCC and triple positive tumor markers, and the independent risk factors for OS were high indocyanine green retention rate at 15 min value, maximum tumor size and triple positive tumor markers. Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers. Conclusion Triple positive tumor markers for early stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early stage HCC.

Background Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients. Methods From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count 600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). Conclusion A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement.

Postoperative pancreatic fistula is a known complication after pancreaticojejunostomy. When an anastomosis collapses completely, two-stage reconstruction is necessary. Herein, we describe the case of a 70-year-old woman who underwent subtotal stomach-preserving pancreaticoduodenectomy with pancreaticojejunostomy after she had developed a severe postoperative pancreatic fistula. The pancreaticojejunostomy was divided, and an external pancreatic drainage tube was placed. Four months later, fistulojejunostomy between the pancreas and the stump of the jejunum was performed successfully using intraoperative gastrojejunoscopy.

We have investigated the thermal unfolding of bovine alpha-lactalbumin by means of circular dichroism spectroscopy in the far- and near-ultraviolet regions, and shown that the native alpha-lactalbumin undergoes heat and cold denaturation. The guanidine hydrochloride-induced unfolding of alpha-lactalbumin was also investigated by circular dichroism spectroscopy at various temperatures from 261 to 318 K. It is shown that the population of the molten globule state is strongly dependent on temperature and that the molten globule state does not accumulate during the guanidine hydrochloride-induced unfolding transition at 261 K. Our results indicate that the molten globule state of alpha-lactalbumin undergoes cold denaturation as the native alpha-lactalbumin does, and that the heat capacity change of unfolding from the molten globule to the unfolded state is positive and significant. The present results further support the idea that the molten globule and the unfolded states do not belong to the same thermodynamic state, and that the native, molten globule and unfolded states are sufficient for interpreting the guanidine hydrochloride-induced unfolding behavior of alpha-lactalbumin.

Pancreatic cancer rarely develops cystic ovarian metastasis. We present a 63-year-old female patient with unresectable pancreas head cancer. Seven months after the introduction of the chemoradiotherapy, a giant intrapelvic cystic tumor with rapid growth was found. The tumor was resected because the patient complained of severe bloating and no other new metastatic sites could be identified. Postoperative pathological examination diagnosed it as an ovarian metastasis from the pancreas cancer.

A young man, aged 24, was investigated because of progressive abdominal distension. On examination, he had a large mass in the mid-abdomen. A contrast-enhanced computed tomography (CT) scan revealed a mass, 25 x 17 x 11 cm, in the mid-abdomen as shown on the axial and coronal scans in Figure 1. The mass had a heterogeneous appearance but many areas of the mass were of low-density consistent with fat. The preoperative diagnosis was that of a retroperitoneal liposarcoma. Laparotomy revealed a relatively firm tumor with a smooth surface (Figure 2). The mass appeared to arise from the body of the pancreas with sparing of the tail of the pancreas (arrowheads). A resection of the body of the pancreas was performed with a pancreaticogastrostomy for the distal pancreatic remnant. At histology, the diagnosis was that of a myxoid pancreatic liposarcoma with surgical margins that were free of tumor. After 44 months, a second operation was performed to remove a local recurrence, 4 x 3 cm in size. He is currently asymptomatic after 3 further months of follow-up. Liposarcomas are malignant neoplasms of adipose tissue. Histologically, the most common types are the well-differentiated liposarcoma, the myxoid liposarcoma and the dedifferentiated liposarcoma. These tumors largely develop in middle-aged or older individuals. Common sites for the dedifferentiated liposarcoma include the retroperitoneum and the spermatic cord. In contrast, well-differentiated and myxoid liposarcomas usually occur in subcutaneous and intramuscular sites and are uncommon in the retroperitoneum. Retroperitoneal liposarcomas, in particular, are often relatively large at the time of diagnosis and only rarely arise from the pancreas. The behavior of liposarcomas is strongly influenced by the histology such that the dedifferentiated liposarcoma is more likely to recur locally and metastasize. The most important factor influencing prognosis is the adequacy of surgical resection at the time of primary presentation. The CT scan illustrated above is typical of a liposarcoma with low density areas consistent with fat as well as thick septae of soft tissue. Dedifferentiated neoplasms have less fat and can have a similar appearance to other sarcomas. The differential diagnosis on imaging may also need to include benign lipoma, angiomyolipoma and malignant fibrous histiocytoma.

Choledochal cysts are congenital anomalies of the bile duct that result in dilatation of the extrahepatic bile duct, the intrahepatic bile ducts or both components of the biliary system. Although several forms of dilatation have been described including bile duct diverticula, the most common is diffuse dilatation of the extrahepatic bile duct. The majority of these patients also have an anomalous junction of the bile duct and main pancreatic duct creating a “long common channel”. At least 50% of patients are diagnosed before the age of 10 years because of abdominal pain, jaundice, pancreatitis or a palpable abdominal mass. However, 25% of patients present as adults, usually with abdominal pain, pancreatitis or abnormal liver function tests. The diagnosis is readily made on an ultrasound study but additional investigations can include computed tomography (CT) scans, magnetic resonance imaging (MRI) scans and endoscopic retrograde cholangiopancreatography. The treatment of choice is usually surgical excision of the cyst with a biliary reconstruction using a choledochojejunostomy. Complications of untreated choledochal cysts include biliary cirrhosis, portal hypertension and the development of cholangiocarcinoma. Complications after surgery can include a cystic bile duct remnant as illustrated below. The patient was a 48-year-old woman who was admitted to our hospital with upper abdominal pain. Her past history included excision of a choledochal cyst at the age of 8 years. She was investigated with an enhanced CT scan, MRI scan (T2 weighted) and magnetic resonance cholangiopancreatography (MRCP). The CT scan (Figure 1, left) and MRCP (Figure 1, right) show a cystic structure in the head of the pancreas with a filling-defect, 15 mm in diameter. Various tumor markers were within the reference range. At laparotomy, there was a dilated remnant of the bile duct in the head of the pancreas (Figure 2, left). This was resected down to the junction with the main pancreatic duct. The bile duct remnant contained a calculus (Figure 2, right) while histological examination of the wall of the sac only revealed chronic inflammatory tissue. The patient has been followed for 12 months since surgery and is currently painfree. The management of enlarged but asymptomatic bile duct remnants is less clear although there are case reports of the development of bile duct cancer.

A new method for producing ultra fine aperture grilles for CDTs has been developed. This new approach can produce 0.125mm pitch aperture grille for 21-in 200-dpi ultra fine CDTs while providing the same optical transmittance and white uniformity as those of conventional ones. Good narrow aperture performance is combined with an excellent smoothness of grille edges. This technology also allows a range of finer pitch shadowmasks as well as aperture grilles to be made practical for further high resolution CDTs.