Ichiro Hirai

Perineural invasion in pancreatic cancer

Introduction Perineural invasion is regarded as a factor associated with local recurrence of pancreatic cancer. Aim To examine perineural invasion of pancreatic cancer pathologically and clinically. Methodology In 24 cases of surgically resected pancreatic cancer, correlations among the degree of perineural invasion, differentiation, interstitial connective tissue, lymph node metastasis, and survival rate were examined. Consecutive 5-&mgr;m serial sections (n = 1072) were made in six cases that showed characteristic mode of perineural invasion. Results Perineural invasion was observed in 17 cases (70.8%; ne0–7; ne1–6; ne2–9; and ne3–2 cases). Perineural invasion was absent in three of five cases of papillary carcinoma, but was observed in 12 of 14 cases of moderately differentiated carcinoma. The survival rate for ne0 was better than that of the other groups, with the 3-year survival rate being 57.1%. Perineural cancer glands had developed discontinuously in two cases. Conclusions Perineural invasion is an important prognostic factor in pancreatic cancer, increasing as the cancer becomes undifferentiated. Even if there are no cancer cells at the margin of the pancreas at the time of surgery, the cancer cells may spread further to the noncancerous pancreas or retroperitoneum. Sufficient dissection of the neural plexus or intraoperative radiation may be required.

A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (japanese) using a web-based data entry system: The 30-day and in-hospital mortality rates for pancreaticoduodenectomy

Objective:To create a mortality risk model after pancreaticoduodenectomy (PD) using a Web-based national database system. Background:PD is a major gastroenterological surgery with relatively high mortality. Many studies have reported factors to analyze short-term outcomes. Subjects and Methods:After initiation of National Clinical Database, approximately 1.2 million surgical cases from more than 3500 Japanese hospitals were collected through a Web-based data entry system. After data cleanup, 8575 PD patients (mean age, 68.2 years) recorded in 2011 from 1167 hospitals were analyzed using variables and definitions almost identical to those of American College of Surgeons–National Surgical Quality Improvement Program. Results:The 30-day postoperative and in-hospital mortality rates were 1.2% and 2.8% (103 and 239 patients), respectively. Thirteen significant risk factors for in-hospital mortality were identified: age, respiratory distress, activities of daily living within 30 days before surgery, angina, weight loss of more than 10%, American Society of Anesthesiologists class of greater than 3, Brinkman index of more than 400, body mass index of more than 25 kg/m2, white blood cell count of more than 11,000 cells per microliter, platelet count of less than 120,000 per microliter, prothrombin time/international normalized ratio of more than 1.1, activated partial thromboplastin time of more than 40 seconds, and serum creatinine levels of more than 3.0 mg/dL. Five variables, including male sex, emergency surgery, chronic obstructive pulmonary disease, bleeding disorders, and serum urea nitrogen levels of less than 8.0 mg/dL, were independent variables in the 30-day mortality group. The overall PD complication rate was 40.0%. Grade B and C pancreatic fistulas in the International Study Group on Pancreatic Fistula occurred in 13.2% cases. The 30-day and in-hospital mortality rates for pancreatic cancer were significantly lower than those for nonpancreatic cancer. Conclusions:We conducted the reported risk stratification study for PD using a nationwide surgical database. PD outcomes in the national population were satisfactory, and the risk model could help improve surgical practice quality.

Multicenter study of serous cystic neoplasm of the Japan pancreas society.

Objectives There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet. Methods In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed. Results Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities. Conclusions Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCNs related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.

Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein: techniques and its significance.

BackgroundPreservation of the spleen in distal pancreatectomy has recently attracted considerable attention. Since our first trial and success with spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis, this procedure (Kimura’s procedure) has been performed very frequently.MethodsThe techniques for spleen-preserving distal pancreatectomy (SpDP) with conservation of the splenic artery and vein are clarified. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane (fusion fascia of Toldt). The connective tissue membrane is cut longitudinally above the splenic vein. It is important to remove the splenic vein from the pancreas by working from the body of the pancreas toward the spleen (median approach), because it is very difficult to remove it in the other direction. The pancreas is removed from the splenic artery by proceeding from the spleen toward the head of the pancreas.ResultsPreservation of the spleen offers various advantages. The maximum platelet levels in blood serum are significantly lower in postoperative patients with splenic preservation than in those with splenectomy. The platelet count was maximal on postoperative day 10 in the 16 patients with SpDP and the count was maximal on postoperative day 13 in the 16 patients with distal pancreatectomy with splenectomy (DPS), and there was a smaller increase in the patients with SpDP than in the patients with DPS. Postoperative bleeding from an ablated splenic artery and vein in SpDP has not been encountered. Either DPS or spleen preservation without preservation of the splenic artery and vein may reduce the blood supply to the residual proximal stomach after distal gastrectomy, which is different from the findings in the Kimura procedure.ConclusionIn SpDP, a very slight elevation of the platelet count in serum may help to prevent infarction of the lungs and brain compared to DPS. Another advantage of SpDP performed according to our procedure is that the blood supply to the proximal stomach is conserved in patients with SpDP who undergo distal gastrectomy with resection of the left gastric artery. Benign lesions, as well as low-grade malignancy of the body and tail of the pancreas, may be indications for this procedure. Surgeons should know the techniques and significance of SpDP with conservation of the splenic artery and vein, which is a very safe and reliable method.

Intraductal Papillary-mucinous Neoplasms of the Gastric and Intestinal Types May Have Less Malignant Potential Than the Pancreatobiliary Type

Objectives: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are classified into 4 types-gastric, intestinal, pancreatobiliary, and oncocytic-on the basis of their morphology and immunohistochemistry. We classified IPMNs at our institute and used this classification to determine the clinicopathological features, prognosis, and malignant potential of the 4 types. Methods: Sixty-one patients with IPMN who underwent surgery between 2000 and 2007 were evaluated retrospectively. Results: There were 24 tumors of the gastric type, 22 intestinal, 12 pancreatobiliary, and 3 oncocytic. Patients with the intestinal or gastric type had a better prognosis than those with the pancreatobiliary type. The intestinal and pancreatobiliary types had almost the same frequencies of carcinoma, but the intestinal type tended to have a lower frequency of invasive carcinoma than the pancreatobiliary type. Patients with invasive carcinomas derived from intestinal-type IPMNs tended to have a better prognosis than those whose invasive carcinomas were derived from the pancreatobiliary type. Conclusions: Intraductal papillary-mucinous neoplasm of the gastric and intestinal types may have less malignant potential than that of the pancreatobiliary type. Invasive carcinomas derived from intestinal-type IPMNs may be less invasive and slower growing than those derived from the pancreatobiliary type.

Pancreatic schwannoma: Case report and an updated 30-year review of the literature yielding 47 cases

Pancreatic schwannomas are rare neoplasms. Authors briefly describe a 64-year-old female patient with cystic pancreatic schwannoma mimicking other cystic tumors and review the literature. Databases for PubMed were searched for English-language articles from 1980 to 2010 using a list of keywords, as well as references from review articles. Only 41 articles, including 47 cases, have been reported in the English literature. The mean age was 55.7 years (range 20-87 years), with 45% of patients being male. Mean tumor size was 6.2 cm (range 1-20 cm). Tumor location was the head (40%), head and body (6%), body (21%), body and tail (15%), tail (4%), and uncinate process (13%). Thirty-four percent of patients exhibited solid tumors and 60% of patients exhibited cystic tumors. Treatment included pancreaticoduodenectomy (32%), distal pancreatectomy (21%), enucleation (15%), unresectable (4%), refused operation (2%) and the detail of resection was not specified in 26% of patients. No patients died of disease with a mean follow-up of 15.7 mo (range 3-65 mo), although 5 (11%) patients had a malignancy. The tumor size was significantly related to malignant tumor (13.8 ± 6.2 cm for malignancy vs 5.5 ± 4.4 cm for benign, P = 0.001) and cystic formation (7.9 ± 5.9 cm for cystic tumor vs 3.9 ± 2.4 cm for solid tumor, P = 0.005). The preoperative diagnosis of pancreatic schwannoma remains difficult. Cystic pancreatic schwannomas should be considered in the differential diagnosis of cystic neoplasms and pseudocysts. In our case, intraoperative frozen section confirmed the diagnosis of a schwannoma. Simple enucleation may be adequate, if this is possible.

Surgical management of pancreatic neuroendocrine tumors

This study outlines the surgical management and clinicopathological findings of pancreatic neuroendocrine tumors (P-NETs). There are various surgical options, such as enucleation of the tumor, spleen-preserving distal pancreatectomy, distal pancreatectomy with splenectomy, pancreatoduodenectomy, and duodenum-preserving pancreas head resection. Lymph node dissection is performed for malignant cases. New guidelines and classifications have been proposed and are now being used in clinical practice. However, there are still no clear indications for organ-preserving pancreatic resection or lymph node dissection. Hepatectomy is the first choice for liver metastases of well-differentiated neuroendocrine carcinoma without extrahepatic metastases. On the other hand, cisplatin-based combination therapy is performed as first-line chemotherapy for metastatic poorly differentiated neuroendocrine carcinoma. Other treatment options are radiofrequency ablation, transarterial chemoembolization/embolization, and liver transplantation. Systematic chemotherapy and biotherapy, such as that with somatostatin analogue and interferon-α, are used for recurrence after surgery. The precise surgical techniques for enucleation of the tumor and spleen-preserving distal pancreatectomy are described.

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms

AbstractBackground: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. Aims: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. Methodology: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Results: Significant differences in the expression of MUC1 and MUC2 were observed between IPMN-adenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p=0.001 and p=0.005, respectively; MUC2: p=0.002 and p<0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p=0.015). Conclusions: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis.

Aim/Background. MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis.Methods. Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically.Results. The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival.Conclusion. The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.