According to the recent international consensus statement, cancer cachexia is defined as "a multifactorial syndrome due to an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support and it leads to progressive functional impairment". Its pathophysiology is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. In addition to cancer cachexia, pancreatic exocrine and endocrine insufficiency causes remarkable weight loss and worsens the prognosis in patients with the unresectable pancreatic cancer. In order to improve the prognosis of unresectable pancreatic cancer, we evaluated the efficacy of elemental diet therapy. Patients were divided into 2 groups: ED group, defined as patients who are able to take 2 packs of elemental diet (Elental^®) more than 12 weeks, and Non-ED group as others. As a result, body weight loss was significantly lower in the ED group and overall survival was significantly longer than that of Non-ED group. Elemental diet therapy for unresectable pancreatic cancer is one of the supportive therapies and contributes towards the overall survival through weight stabilization.

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In recent years, prognosis of patients with unresectable locally advanced pancreatic cancer (LAPC) has improved because of improvements in chemoradiotherapy (CRT) or chemotherapy. Several clinical studies on CRT or chemotherapy have shown favorable efficacy with median survival more than 15 months. In addition, some studies have reported the use of CRT or chemotherapy to convert unresectable disease to resectable status in patients with LAPC. However, there is still limited evidence for the treatment of LAPC, and the role of CRT remains controversial. In this report, we reviewed the outcome of CRT in our facilities, and considered the significance of non-surgical treatment for LAPC. The median survival time was 15.4 months, and 3-year and 5-year survival rate were 17.5% and 6.7%, respectively. There were some long-term survivors after CRT in our cohort of patients. In this report, we also reviewed the outcome of surgery after CRT or chemotherapy in patients with LAPC, and considered the significance of such multidisciplinary approach to improve patient outcome.

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From the view point of oncology and preservation of pancreatic function, distal pancreatectomy (DP) is an appropriate radical surgery for cancer in the pancreatic body and tail. The gastroduodenal artery is considered as a border of the resection area for distal pancreatectomy; therefore, total pancreatectomy (TP) and pancreatoduodenectomy (PD) are often performed as radical surgical methods for patients with pancreatic caners in the central pancreas near the gastroduodenal artery. However, TP abolishes all of the pancreatic functions, and PD is not curative enough for the pancreatic cancer located left to the portal vein. We here present our early experiences of extensive distal pancreatectomy (ExDP), which enables DP for patients with pancreatic cancer around the gastroduodenal artery, as a new surgical procedure for the cancer in the central pancreas.

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We perform distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) without arterial reconstruction for locally advanced cancer of the pancreatic body involving the common hepatic artery and/or celiac axis with perineural invasion in the nerve plexus surrounding the arteries. DP-CAR has been performed in patients in whom the gastroduodenal artery and superior mesenteric artery could be preserved. Between April 1998 and December 2009, 53 patients underwent DP-CAR in our institution. The surgical margins were histologically clear (R0) in 49 (92%) patients. The postoperative morbidity rate was 62%. Estimated overall 1- and 3-year survival rates were 76% and 37%, respectively, and the median survival was 25 months. After surgery, contrary to expectations, postoperative diarrhea was not severe but mild. Moreover, preoperative intractable abdominal and/or back pain disappeared immediately. In principle, since 2006, patients who have undergone DP-CAR also received postoperative adjuvant chemotherapy. Patients could achieve a favorable general status with in about 2 months after DP-CAR enough to be able to start adjuvant chemotherapy. To shorten the period before chemotherapy, adequate management of symptoms should be performed in order to decrease the postoperative morbidity rate.

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The aim of this study was to evaluate the surgical management for the pancreatic cancer from the point of view of the curability and function. A total of 570 patients who underwent pancreatectomy for invasive ductal adenocarcinoma of the pancreatic head between 1981 and 2010 were reviewed by decade retrospectively. Patients were divided into three groups; first decade (1981-1990, n=172), middle decade (1991-2000, n=194) and last decade (2001-2010, n=204). Patients with severe invasion to the SMA nerve plexuses were included for surgical indication in the first decade, but were excluded for surgical indication in the middle and last decades. Circle dissection of the SMA nerve plexuses was performed in the first decade, but right-side dominant semicircle dissection was performed in the middle and last decades. Prophylactic dissection of the paraaortic lymph nodes (No. 16) was performed in the first and middle decades, but not in the last decade. Stomach preserving procedure was performed in the middle and last decades, but not in the first decade. Intraoperative radiotherapy (IORT) was performed in the first decade and adjuvant chemotherapy was performed in the last decade, but no adjuvant therapy was performed in the middle decade. There was no difference in the prevalence of Stage I/II/III and IVa/IVb between the three groups. Rates of the stomach preserving procedure were 10% in the first decade, 70% in the middle decade and 88% in the last decade. Rates of R0 resection were 47%, 53% and 72%, respectively. Incidence rates of severe diarrhea were 23%, 8%, 5%, and the incidence rates of delayed gastric emptying (DGE) in the patients with stomach-preserving procedure were 29%, 10%, 3%, respectively. Median survival time (MST), 3-year survival rate, 5-year survival rate were 9.4 months, 7.0%, 6.4% in the first decade, 15.4 months, 20.0%, 17.2% in the middle decade and 26.3 months, 40.6%, 33.6% in the last decade. In conclusion, the appropriate surgical indication, R0 resection, stomach preserving procedure and adjuvant chemotherapy could make it possible for good quality of life and long-term survival for patients with pancreatic head cancer.

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Long-term survival after pancreatic surgery has increased gradually due to recent improvements in surgical techniques and experiences. We investigated fat absorptive function and glucose metabolism of post pylorus preserving pancreatoduodenectomy (PPPD) and DP (Distal pancreatectomy). The cumulative percent dose of ¹³C (7h) was performed for patients undergoing PPPD and 12 healthy volunteers. Percent dose ¹³C cum 7h was significantly lower in patients with PPPD (6.8±4.8%) than in healthy controls (15.5±6.0%; P<0.01). The degree of pancreatic exocrine cells was calculated as ratio of the area of pancreatic exocrine cells to the total area measured in the entire section. The histological degree of pancreatic exocrine cells was useful for predicting postoperative fat absorptive function after PPPD. The cumulative percent dose of ¹³C (7h) was not significantly different between patients with DP (9.7±3.2%) and healthy controls (13.3±5.9%). Preoperatively, 14 (35%) patients were diabetic (HbA1c ≥6.9%) and 26 (65%) were non-diabetic. In the non-diabetic patients, the level of HbA1c was significantly higher before DP than after DP (P=0.01). Of the non-diabetic patients before DP operation (26/40), 46% of these patients (12/26) developed impaired glucose tolerance within one year after DP. ¹³C-breath test and histological degree of pancreatic exocrine cells reliably show long-term fat absorptive function after PPPD. The preoperative HbA1c is predictive value for glucose metabolism disturbance after for patients after DP. These might be clinically useful methods for long-term pancreatic function and long-term survival after pancreatic surgery.

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Background: The aim of this study was to evaluate the changes in pancreatic function following long-term survivors with curative resection for pancreatic cancer.
Methods: 13 patients survived more than five years after curative resection for pancreatic cancer to 2010 from 100 patients with resection of pancreatic cancer. Physiological pancreatic functions, use of anti-indigestion drugs, changes of diabetes mellitus (DM), Body Mass Index (BMI), total protein, albumin, and hemoglobin were retrospectively investigated in long-term survivors.
Results: Extent of disease were: pancreas head 9 patients, and body/tail 4 patients. Operative procedures were: PPPD 8 patients, PD 1 patients, and DP 4 patients. Total excision of the remnant pancreas was performed in 2 patients of PPPD, and 1 of DP during following up. Patients took anti-indigestion drugs during 1 year after surgery and did not take a medicine for diarrhea. Diabetes mellitus developed in 23.1% after surgery. BMI decreased over 3 years after surgery. Total protein and hemoglobin were not different before and after surgery. Albumin decreased over 5 years after surgery.
Conclusions: It is important to perform postoperative adjuvant chemotherapy early to time with the preservation of pancreatic function for long-term survivors with curative resection for pancreatic cancer.

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We investigate the incidence of diabetes mellitus (DM) in patients with pancreatic cancer before and after pancreatoduodenectomy (n=91) or distal pancreatectomy (n=36). Thirty-four patients (37%) had DM before pancreatoduodenectomy, and 36 patients (40%) had DM after pancreatoduodenectomy. Twelve patients (33%) had DM before distal pancreatectomy, and 22 patients (61%) had DM after distal pancreatectomy. Patients that undergo distal pancreatectomy are more likely to develop DM than those who undergo pancreatoduodenectomy.

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A 50-year-old woman with acute recurrent pancreatitis was found to have biliary type sphincter of Oddi dysfunction (SOD) with pancreas divisum. Abdominal ultrasonography and dynamic computed tomography showed that the common bile duct and pancreatic duct were not dilated. Hepatobiliary scintigraphy showed delayed biliary drainage. Endoscopic retrograde pancreatography via the accessory papilla showed no dilatation of the isolated dorsal pancreatic duct, indicating that pancreas divisum was present. The patient underwent endoscopic minor papillotomy and endoscopic sphincteromy. Later, additional treatment of endoscopic papillary balloon dilatation was required, and then symptoms were improved. A search of PubMed turned up no report of concomitant SOD and pancreas divisum. SOD with pancreas divisum is extremely rare.

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A 42-year-old man was admitted to our department after detection of pancreatic duct dilatation on ultrasonography. Magnetic resonance cholangiopancreatography showed stenosis of the main pancreatic duct in the pancreatic body, and the pancreatic duct in the pancreatic tail was also dilated to a diameter of 10mm. No clear tumor was detected on ultrasonography, multidetector computed tomography, or endoscopic ultrasonography. Endoscopic retrograde pancreatography showed severe circumferential stenosis 3mm in length, localized to the pancreatic body. Pancreatic juice cytology yielded negative results, and although causes such as pancreatic duct inflammation were considered, middle pancreatectomy was performed because the possibility of carcinoma in situ could not be ruled out. Severe fibrosis was observed in the pathological tissue around the stenosis site, which contained vesicles arranged in cords along the stenosed pancreatic duct as well as a node 5mm in diameter resulting from the extensive fibrosis. Immunostaining showed positive results for chromogranin A and serotonin, and neuroendocrine tumor was diagnosed. A search of the literature revealed only 14 reports from Japan of pancreatic neuroendocrine tumor ≤20mm in diameter resulting in pancreatic duct stenosis, indicating the extreme rarity of this condition. Fibrosis caused by serotonin was thought to be involved in the pathogenesis of pancreatic duct stenosis in this case.

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A 44-year-old man with a history of chronic pancreatitis was admitted to the local hospital because of a severe back pain. The patient presented with sudden hematemesis on the day after admission and bleeding from the papilla vater was confirmed after an emergency esophagogastroduodenoscopy. Contrast CT and MR angiography revealed a pseudocyst, associated with chronic pancreatitis, in contact with the inferior pancreaticoduodenal artery (IPDA) that was bleeding into the cyst; the patient was then referred to our hospital. Dynamic CT clearly revealed a pseudoaneurysm of 7.7mm in diameter seen in the IPDA. We performed transcatheter arterial embolization (TAE) to control the bleeding. The distal and proximal segments of the pseudoaneurysm were embolized with tornado micro coil. The patient was discharged without postoperative complications. HP is relatively rare, and few have reported pseudoaneurysm of the IPDA as the cause.

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A 52-year-old woman was referred to our hospital because of tumors of the head of the pancreas. Ten years earlier, she had undergone surgical resection (enucleation) of the calcitonin-secreting, neuroendocrine tumor of the head of the pancreas. The preoperative serum value of calcitonin was 438pg/ml and immunohistochemical examination of the tumor showed strong positivity for calcitonin. This time, enhanced abdominal CT revealed existence of 4 isovascular tumors (diameter of 4cm, 1cm, 2cm, 2cm, respectively) in the head of the pancreas. These tumors seemed to be multiple pancreatic endocrine tumors occurring at the same site that the calcitonin-secreting endocrine tumor had existed 10 years earlier. Complete resection by pylorus-preserving pancreaticoduodenectomy was performed. Immunohistochemical examination of the tumors showed positivity for neuroendocrine markers such as chromogranin A, although no stain was seen for any hormone markers including calcitonin. These tumors were diagnosed as pancreatic neuroendocrine tumor (NET) G2 by the new WHO classification. The calcitonin-secreting pancreatic neuroendocrine tumor is extremely rare, and this seemed to be an interesting case for the thinking about the classification of nonfunctioning tumors as either recurrence or second primary tumors.

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