A case of API2-MALT1-positive gastric MALT lymphoma with concomitant diffuse large B-cell lymphoma.

API2-MALT1 translocation-positive gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphoma is thought to transform to diffuse large B-cell lymphoma (DLBCL) rarely. A 69-year-old man presented with epigastralgia. Esophagogastroduodenoscopy showed multiple ulcerations in the stomach. Endoscopic biopsies revealed MALT lymphoma, with Helicobacter pylori infection. The patient underwent eradication therapy with no improvement, and was thereafter followed without additional therapy at his request. Twelve years after initial diagnosis, follow-up computed tomography (CT) showed multiple nodules in bilateral lungs, and a needle biopsy revealed MALT lymphoma, the same as in the stomach and API2-MALT1 translocation was found. Because he again refused additional therapy, follow-up was continued. 15 years after initial diagnosis, CT showed lymphadenopathy at the splenic hilum. At first we suspected disease progression of gastric MALT lymphoma, however a needle biopsy revealed DLBCL without API2-MALT1. Thus, the tumor at the splenic hilum was finally diagnosed as a de novo DLBCL as a second malignancy. Although treatment with rituximab given his age and his wishes was attempted, he died of DLBCL 15 years after the initial diagnosis. We experienced an API2-MALT1-positive gastric MALT lymphoma with concomitant DLBCL, not transformed to DLBCL over a 15-year clinical course.

Optimal intake of clear liquids during preparation for afternoon colonoscopy with low-volume polyethylene glycol plus ascorbic acid.

BACKGROUND AND STUDY AIMS: The standard colonoscopy preparation regimen in Japan for afternoon procedures is sequential intake of 1 L of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC), 0.5 L of clear liquid, 0.5 L of PEG-ASC, and finally 0.25 L of clear fluids (all at a rate of 0.25 L every 15 min). However, this regimen seems poorly tolerated and complicated for many patients compared to previous regimen of polyethylene glycol electrolyte lavage solution. The aim of this study was to evaluate an alternate regimen of 0.5 L of PEG-ASC followed by 0.25 L clear liquids, repeated 3 times. PATIENTS AND METHODS: This was a single-blinded, non-inferiority, randomized controlled study. Subjects were randomized to the standard regimen or the alternate regimen using a web-based registry system. All patients were instructed to eat a pre-packaged, low residue diet and to take sodium picosulfate hydrate the day before colonoscopy. The Boston Bowel Preparation Scale was used to evaluate bowel cleansing, and a 3-point scale was used to assess mucosal visibility. The primary endpoint was successful bowel cleansing. The acceptability, tolerability, safety, and endoscopic findings of these two regimens were secondary endpoints. RESULTS: A total of 409 patients were randomized to either the standard regimen (n = 204, males 54.0 %, mean age 65.5 years) or the alternate regimen (n = 205, 54.6 %, 65.0 years). The rates of successful bowel cleansing were 71.1 % (64.3 - 77.2 %) with the standard regimen vs. 75.1 % (68.6 - 80.9 %) with the alternate regimen (95 % lower confidence limit, for the difference = - 4.6, non-inferiority P  < 0.05). No significant differences were found in tolerability, safety, and endoscopic findings. CONCLUSION: The alternate regimen and standard regimen are clinically equivalent with respect to cleansing efficacy and acceptability, tolerability, safety, and endoscopic findings. These results are good news for patients with difficulty drinking the first liter of PEG-ASC.

The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome.

A young woman with Li-Fraumeni syndrome (LFS) was referred to our hospital. On examination, multiple flat neoplasms were detected in addition to semi-pedunculated polyps. Restorative proctocolectomy was performed; one submucosal invasive cancer, two mucosal cancers, and several adenomas with high-grade dysplasia were detected. On immunohistochemical staining with p53, every part of all neoplasms, even the small adenomas, showed strong positive staining. Multiple flat neoplasms may be characteristic of patients with LFS and may have a much higher risk of rapid progression to invasive carcinomas than sporadic neoplasms. Thus, careful and frequent colonoscopy surveillance may be needed for patients with LFS.

Treatment of biliary strictures with fully covered self-expandable metal stents after pancreaticoduodenectomy.

Background and study aims Anastomotic stricture is a late complication after biliary reconstructive surgery, but standard treatments are currently lacking. We selected patients who had undergone pancreaticoduodenectomy and Child's procedure, and aimed to evaluate the safety and efficacy of temporary placement of fully covered self-expandable metal stents (FCSEMSs) to treat postoperative anastomotic stricture. Patients and methods This study retrospectively analyzed 13 patients who underwent treatment with FCSEMSs for anastomotic stricture between June 2011 and March 2016. We evaluated technical and clinical success, complications, duration of patency after FCSEMS removal, and re-stenosis. Results All of the anastomotic strictures were improved by FCSEMS placement and luminal patency was maintained throughout the follow-up period, with no complications. After 2 months, the FCSEMSs were removed endoscopically in nine patients, and in four patients the stent had been expelled spontaneously per rectum. Median duration of follow-up was 225 days (range 30 - 935 days). No re-stenosis occurred in any of the 13 cases following stent removal. Conclusion Deployment of FCSEMSs for anastomotic stricture offers a safe and promising treatment that may replace percutaneous transhepatic biliary drainage and deployment of multiple plastic stents as the first-line treatment.

Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study.

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC. METHODS: We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed. RESULTS: Median overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40). CONCLUSIONS: The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.

Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: A retrospective cohort study.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC. METHODS: A total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL. RESULTS: Median RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p < 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p < 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was >1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value. CONCLUSIONS: The present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.

Endoscopic ultrasonography-guided biliary drainage: Who, when, which, and how?

Both endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) and EUS-guided hepaticogastrostomy (EUS-HGS) are relatively well established as alternatives to percutaneous transhepatic biliary drainage (PTBD). Both EUS-CDS and EUS-HGS have high technical and clinical success rates (more than 90%) in high-volume centers. Complications for both procedures remain high at 10%-30%. Procedures performed by endoscopists who have done fewer than 20 cases sometimes result in severe or fatal complications. When learning EUS-guided biliary drainage (EUS-BD), we recommend a mentor's supervision during at least the first 20 cases. For inoperable malignant lower biliary obstruction, a skillful endoscopist should perform EUS-BD before EUS-guided rendezvous technique (EUS-RV) and PTBD. We should be select EUS-BD for patients having altered anatomy from malignant tumors before balloon-enteroscope-assisted endoscopic retrograde cholangiopancreatography, EUS-RV, and PTBD. If both EUS-CDS and EUS-HGS are available, we should select EUS-CDS, according to published data. EUS-BD will potentially become a first-line biliary drainage procedure in the near future.

Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms.

BACKGROUND: Multiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling. METHODS: From 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis. RESULTS: Of the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3 %, respectively; including the six suggestive cases, diagnostic values were 94.8 % sensitivity (55/58), 99.4 % specificity (350/352), and 98.7 % accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR) = 10.0] and in tumor-rich stromal fibrosis (OR = 10.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors. CONCLUSIONS: EUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy.

A Randomized Controlled Trial Evaluating a Low-Volume PEG Solution Plus Ascorbic Acid versus Standard PEG Solution in Bowel Preparation for Colonoscopy.

Evaluation of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC) has been controversial in the point of its hyperosmolarity, especially in old population. So we therefore designed the present study to compare the efficacy, acceptability, tolerability, and safety of 1.5 L PEG+ASC and 2 L standard PEG electrolyte solution (PEG-ELS), not only in the general population, but also in patients of advanced age. Randomization was stratified by age (<70 years or 70> years), and hematological and biochemical parameters were compared in each age group, especially with respect to the safety profile of each regimen. As a result, the 1.5-L PEG-ASC regimen had higher patient acceptability than the 2-L PEG-ELS regimen. Tolerability, bowel cleansing, and safety were similar between regimens. However, we demonstrated significant statistical changes in the hematological and biochemical parameters after taking bowel preparation solutions, not only in the PEG+ASC group, but also in the PEG-ELS group. No significant differences in the safety profile were found between subjects aged less than 70 years and those aged 70 years or more; nevertheless, regardless of age, proper hydration is needed throughout the bowel preparation process.

Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?

BACKGROUND: The WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. METHODS: We retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes. RESULTS: The median Ki67 LI was 69.1% (range 40-95%). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: hypervascularity on CT, 50% (2/4) vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40-53%) vs. 85% (54-95%) (P = 0.001); Rb immunopositivity, 100% (4/4) vs. 14% (1/7) (P = 0.015); KRAS mutations, 0% (0/4) vs. 86% (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0% (0/2) vs. 100% (4/4) (P = 0.067), and median survival, 227 vs. 186 days (P = 0.227). CONCLUSIONS: The WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted.

Immunoglobulin G4-related disease with scant tissue IgG4.

A 56-year-old man was admitted to our hospital for renal dysfunction and symmetrical swelling of submandibular glands. Laboratory and imaging findings were consistent with immunoglobulin G4-related disease (IgG4RD). Histological findings of the submandibular gland and the kidney were also consistent with IgG4RD. However, the patient did not have elevated serum or tissue IgG4 levels. Oral prednisolone therapy, initially 50 mg/day and gradually tapered over 12 months, improved his laboratory abnormalities and the swelling of his affected organs. These findings prompted our final diagnosis of IgG4RD. IgG4RD is a newly recognised disease with an unknown aetiology. This case suggests that IgG4 antibodies do not play a primary role in the aetiology of IgG4RD. Furthermore, clinicians should not exclude the diagnosis of IgG4RD in patients lacking elevated IgG4 levels in their affected tissues, particularly if they have other features of IgG4RD. Steroid therapy should be considered for such patients.

[A case of endocrine carcinoma of the cecum treated with CDDP/VP-16].

A 41-year-old man was admitted to our hospital because of multiple liver tumors. Colonoscopy showed a mass lesion in the cecum. He was given a diagnosis of endocrine cell carcinoma by immunostaining technique, and received chemotherapy of CAPOX regimen for 3 courses. After that, he underwent second-line chemotherapy of EP(CDDP/VP-16)regimen due to deterioration of his performance status(PS), and his tumor marker NSE. He then showed dramatically improved PS, and improvement in the size of liver mets and NSE(4. 3mg/mL).