Treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice: a region-wide analysis.

BACKGROUND: FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have recently been available for treating pancreatic ductal adenocarcinoma (PDAC). We investigated trends in characteristics, treatment and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. METHODS: We retrospectively reviewed the medical records of 1085 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in the Hokuriku area between January 2009 and July 2015. RESULTS: The incidence of pathologically proven PDAC had increased from 18.7% in 2009 to 56.2% in 2015. Oncological therapy was administered to 779 patients (71.8%): chemotherapy (n = 675), chemo-radiotherapy (n = 92) or radiotherapy (n = 12); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 30.7% of the 75 patients diagnosed in 2015 received FFX, 25.3% GnP, 22.7% GEM and 17.3% S-1. The objective response rates of patients treated with FFX, GnP and GEM were 14.9%, 35.0% and 5.5%, respectively and the OS 10.3, 9.9 and 7.5 months after FFX, GnP and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 70.2%, 70.0% and 18.8% of the patients treated with FFX, GnP and GEM, respectively. The reasons for treatment discontinuation were adverse events in 9.8%, 26.7% and 24.1% of the patients treated with FFX, GnP and GEM, respectively. CONCLUSION: Chemotherapeutic protocols changed dramatically between 2009 and 2015. Continuous collection and analysis for our cohort with longer follow-up provides useful information about treatment selection and prediction of outcome.

Pancreatic acinar cell carcinoma with extensive tumor embolism at the trunk of portal vein and pancreatic intraductal infiltration.

A 59-year-old man was admitted to the hospital with acute pancreatitis. The cause was suggested to be a pancreatic tumor based on computed tomography (CT). The pancreatic tumor was 45 mm with an extensive tumor embolism at the trunk of the portal vein and intraductal infiltration of the main pancreatic duct (MPD). The pancreatic tumor was diagnosed as acinar cell carcinoma (ACC) by endoscopic ultrasound guided fine needle aspiration. Therefore, the cause of acute pancreatitis was diagnosed to be intraductal infiltration of ACC in the MPD. Chemotherapy was initially performed because it was difficult to perform surgery due to extensive tumor embolism at the trunk of the portal vein. Degeneration and reduction of ACC and tumor embolism of the portal vein was noted on CT after chemotherapy, and extended distal pancreatectomy with portal vein reconstruction was performed. There has been no relapse for 5 years postoperative follow-up. This is an interesting and rare case because ACC with intraductal infiltration of MPD is low in frequency; most ACCs are asymptomatic when they are found, and many cases tend to have poor prognosis in spite of surgical cases.

A unique case of massive gastrointestinal bleeding.

OBJECTIVES: Lipomas are the second most common benign tumors of the small bowel, and most lipomas are asymptomatic. However, lipomas with diameters of >20 mm tend to be symptomatic, for example, to cause bleeding, obstructive jaundice, abdominal pain, intestinal obstruction, intussusception, and/or perforation. METHODS/RESULTS: We report a case of massive gastrointestinal bleeding from a jejunal lipoma combined with intussusception. A preoperative diagnosis of gastrointestinal bleeding derived from a jejunal lipoma combined with intussusception was made based on double-balloon enteroscopy and contrast-enhanced computed tomography, and partial resection of the small intestine was performed. After surgery, there was no additional gastrointestinal bleeding. CONCLUSION: There have only been a few reports about cases of jejunal lipoma involving simultaneous bleeding and intussusception. Double-balloon enteroscopy is useful for preoperatively diagnosing bleeding from a lipoma. Our case highlights that jejunal lipoma can cause massive unexplained gastrointestinal bleeding.

Gastric adenocarcinoma of the fundic gland (chief cell-predominant type): A review of endoscopic and clinicopathological features.

Gastric adenocarcinoma of the fundic gland (chief cell-predominant type, GA-FG-CCP) is a rare variant of well-differentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.

Gastric adenocarcinoma of fundic gland type: Five cases treated with endoscopic resection.

Recently, a new disease entity termed gastric adenocarcinoma of fundic gland type (GA-FG) was proposed. We treated five cases of GA-FG with endoscopic submucosal dissection. All tumors were small and located in the upper third of the stomach. Four tumors were macroscopically identified as 0-IIa and one was identified as 0-IIb. Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder. All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion. Lymphatic invasion was seen only in one case, while no venous invasion was recognized. All tumors were positive for pepsinogen-I  and MUC6 by immunohistochemistry. None showed p53 overexpression, and the labeling index of Ki-67 was low in all cases. All cases have been free from recurrence or metastasis. Herein, we discussed the clinicopathological features of GA-FG in comparison with past reports.

Overt diabetes mellitus caused by the topical administration of dexamethasone ointment on the oral mucosa.

We herein describe the case of a 68-year-old man who developed overt diabetes mellitus following the topical administration of dexamethasone 0.1%-containing ointment over a five-month period to treat oral lichen planus. The topical dexamethasone therapy was discontinued gradually, and the patient was subsequently treated with insulin for one month without clinical signs of overt adrenal insufficiency. An oral glucose tolerance test revealed impaired glucose tolerance after the treatment. The potential for the deterioration of glucose metabolism must be considered when patients with impaired glucose tolerance are treated with relatively low doses of topical corticosteroid ointment on the oral mucosa, even for short periods.

[A case of hepatic sarcoidosis presenting with cirrhotic symptoms].

A man in 40s with skin sarcoidosis presented with signs and symptoms of liver injury and thrombocytopenia. Enhanced computed tomography and magnetic resonance imaging revealed cholecystolithiasis, hepatic deformation, and giant splenomegaly. Gastrointestinal endoscopy showed esophageal varices. Cholecystectomy, splenectomy, and wedge biopsy of the liver were performed. Histopathology of the liver revealed many granulomas and severe periportal fibrosis without lobular reconstruction. These findings were compatible with hepatic sarcoidosis, but not liver cirrhosis. Here we report a rare case of hepatic sarcoidosis presenting with cirrhotic symptoms.

A pedunculated polyp-shaped small-bowel lymphangioma causing gastrointestinal bleeding and treated by double-balloon enteroscopy.

We report a rare case of a small-bowel lymphangioma causing massive gastrointestinal (GI) bleeding that we successfully diagnosed and treated using double-balloon enteroscopy (DBE). An 81-year-old woman suffering from repeated GI bleeding of unknown origin underwent a capsule endoscopy at a previous hospital. She was suspected of having bleeding from the jejunum, and was referred to our department for diagnosis and treatment. An oral DBE revealed a 20 mm × 10 mm, regularly surfaced, white to yellowish, elongated, pedunculated jejunal polyp with small erosions at 10 cm distal to the ligament of Treiz. Since no other source of bleeding was identified by endoscopy in the deep jejunum, an endoscopic polypectomy (EP) was performed for this lesion. A subsequent histopathological examination of the resected polyp showed clusters of lymphatic vessels with marked cystic dilatation in the submucosa and the deep layer of the lamina propria mucosae. These characteristics are consistent with the typical features of small-bowel lymphangioma with erosions. Although clipping hemostasis was performed during EP, re-bleeding occurred. Finally, a complete hemostasis was achieved by performing an additional argon plasma coagulation.

[A case of hepatocellular carcinoma showed the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology using the cell block technique for differential diagnosis of gastric submucosal tumor].

A mass lesion presenting difficulty in differential diagnosis between a tumor in the lateral segment of the liver and a gastric submucosal tumor (SMT) was found in a 59-year-old man with chronic hepatitis B. For differential diagnosis between the 2 lesions, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was performed. EUS showed a tumor exhibiting a mosaic pattern with a halo derived from the lateral segment of the hepatic left lobe in contact with the stomach. FNA using the cell block technique revealed findings consistent with HCC. No examination-associated complications developed. In patients with HCC that is in contact with the stomach and shows extrahepatically protruding growth, which is difficult to differentiate from gastric SMT, EUS-FNA is a method worthy of trying.

Autoimmune polyglandular syndrome type 3 with anorexia.

A 71-year-old man with diabetes mellitus visited our hospital with complaints of anorexia and weight loss (12 kg/3 months). He had megaloblastic anemia, cobalamin level was low, and autoantibody to intrinsic factor was positive. He was treated with intramuscular cyanocobalamin, and he was able to consume meals. GAD autoantibody and ICA were positive, and he was diagnosed with slowly progressive type 1 diabetes mellitus (SPIDDM). Thyroid autoantibodies were positive. According to these findings, he was diagnosed with autoimmune polyglandular syndrome type 3 with SPIDDM, pernicious anemia, and Hashimoto's thyroiditis. Extended periods of cobalamin deficiency can cause serious complications such as ataxia and dementia, and these complications may not be reversible if replacement therapy with cobalamin is delayed. Although type 1 diabetes mellitus with coexisting pernicious anemia is very rare in Japan, physicians should consider the possibility of pernicious anemia when patients with diabetes mellitus have cryptogenic anorexia with the finding of significant macrocytosis (MCV > 100 fL).

Novel diagnostic method of testing for Helicobacter pylori infection using the rapid leukocyte strip test, Leukostix.

BACKGROUND AND AIM: A characteristic of gastric mucosa infected with Helicobacter pylori is infiltration of inflammatory cells, mainly consisting of neutrophils. The present study aimed to detect neutrophils in homogenates of biopsied gastric mucosa semiquantitatively using the rapid leukocyte strip test, Leukostix. The authors then investigated the association of these results with H. pylori status. METHODS: The authors studied 342 patients undergoing endoscopy. Of these, 160 were treated for eradication of H. pylori infection and were reassessed after treatment. For the definitive diagnosis of H. pylori infection, quantitative culture, the rapid urease test and immunohistostaining were performed. Additionally, serum antibody against H. pylori was determined at the initial examination, and the 13C-urea breath test was performed after treatment. With the use of Leukostix, homogenates of biopsied gastric mucosa were spotted onto strips and judged 2 min later. RESULTS: There was a significant correlation between the positive reaction of Leukostix and the number of neutrophils in gastric tissues determined by microscopic observation. The sensitivity and specificity of Leukostix at the initial examination were 97.9% and 76.9%, respectively, while those after eradication treatment were 100% and 97.2%, respectively. There was a significant positive correlation between the degree of reaction of Leukostix and the amount of H. pylori determined by quantitative culture. CONCLUSIONS: The Leukostix test, using biopsied samples of gastric mucosa, was excellent for quantitative determination of neutrophils and useful for diagnosis of H. pylori infection and early assessment of treatment efficacy. Positive gradations of Leukostix results corresponded closely with the amount of H. pylori in gastric tissues.

Utility and limitations of a method for detecting Helicobacter pylori-specific antigens in the stool.

BACKGROUND: Recently, a method for detecting Helicobacter pylori-specific antigens in the stool (HpSA) has been proposed to be useful clinically. The aim of this study was to determine the accuracy of HpSA for the diagnosis of H. pylori infection, including early assessment after eradication treatment, and the potential for quantitative evaluation of H. pylori in the stomach. METHODS: The subjects were 85 patients with gastroduodenal disorders who underwent endoscopic examination. Of these, 36 were treated for eradication of H. pylori infection and reassessed 4-8 weeks after treatment. HpSA was tested by enzyme immunoassay. For the definitive diagnosis of H. pylori infection, biopsy specimens were taken endoscopically and examined by quantitative culture, rapid urease test, and immunohistostaining. In addition, serum antibody against H. pylori was tested before the eradication treatment and a (13)C-urea breath test was conducted after treatment. The results of these reference tests were compared with those obtained by HpSA. RESULTS: The sensitivity and specificity of HpSA were 90.4% and 100% before eradication treatment and 57.1% and 100% after the treatment. There was a positive correlation between the optical density of HpSA and the number of H. pylori bacilli evaluated by quantitative culture. CONCLUSIONS: The HpSA test is considered to be an accurate method for the diagnosis of H. pylori infection, with high specificity. However, there may be problems of false negativity if HpSA is used for the early assessment of treatment efficacy. Furthermore, HpSA is suggested to have potential for the quantitative evaluation of H. pylori status in the stomach.

Intestinal obstruction in autosomal dominant polycystic kidney disease.

A 42-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital on April 29, 1999, with complaints of abdominal pain. A diagnosis of intestinal obstruction was reached on the basis of clinical findings and X-ray evidence. A computed tomography scan of the abdomen showed massively enlarged kidneys, especially the right kidney, which seemed to compress the small intestine. The patient underwent percutaneous aspiration of the largest cysts on the surface of the right kidney. The symptoms, in this rare case of intestinal obstruction by an enlarged kidney in ADPKD, were alleviated the day after the aspiration procedure.