[Ulcerative colitis diagnosed with facial pyoderma gangrenosum: a case report].

Pyoderma gangrenosum (PG) is a sterile inflammatory skin condition that is frequently associated with immune-related diseases, including inflammatory bowel disease (IBD). PG causes noninfectious ulcers. Facial PG is uncommon while PG usually occurs on the trunk and lower limbs. Herein, we report a case of a male teenager with fever, pustules, ulcers, and necrosis on both cheeks. He was initially diagnosed with complicated acne with bacterial infection, but the condition progressed to subcutaneous ulcers despite treatment. Biopsy revealed inflammatory lesions in dermal and subcutaneous tissue with neutrophil infiltration, consistent with PG. Although lacking typical IBD symptoms, blood tests revealed anemia and positive fecal occult blood. Sigmoidoscopy revealed inflammation, ulcers, and pseudopolyps in the colon and rectum, thereby diagnosing ulcerative colitis (UC). After treating PG and UC with prednisolone and skin grafts, golimumab was prescribed. The patient is now in remission. Necrotic tissue buildup can complicate closure in PG cases;this emphasizes the need for effective IBD treatment to facilitate procedures such as skin grafts.

[Ulcerative colitis complicated by multiple aseptic subcutaneous abscesses: a case report].

A woman in her 40s, previously diagnosed with ulcerative colitis (UC), presented with anterior chest pain. A CT scan of her chest and skin examination showed no abnormal findings. She was initially managed with antibacterial agents, but her chest pain worsened, she developed a fever, and there was an overall deterioration of her general condition. A repeat CT scan found abscesses on the anterior surface of her sternum and gluteal region, and colonoscopy found worsening UC lesions. Her multiple subcutaneous abscesses were aseptic, and she was diagnosed with pyoderma gangrenosum (PG), an extraintestinal manifestation of UC. Steroid treatment was initiated and her overall condition as well as her subcutaneous abscesses improved rapidly. There are only a few case reports of PG without skin manifestation but only subcutaneous aseptic abscesses. However, subcutaneous abscesses may progress to PG with skin ulcers if initial treatment is delayed. Even with non-specific clinical features, prompt diagnosis of relapsed UC with potential extraintestinal manifestations must be considered. This is a rare case and aims to highlight the importance of early diagnosis and treatment of PG, which is an extraintestinal manifestation of relapsed UC.

Cancer-related FGFR2 overexpression and gene amplification in Japanese patients with gastric cancer.

OBJECTIVE: Fibroblast growth factor receptor 2 (FGFR2) has been proposed as a novel druggable target in unresectable gastric cancer. FGFR2 alteration has been reported as associated with poor prognosis even in patients with gastric cancer who received systemic chemotherapy. This study aimed to evaluate the frequency of FGFR2 overexpression and gene amplification in clinical specimens from Japanese patients with recurrent or unresectable gastric cancer. METHODS: This observational study enrolled patients who were histologically or cytologically confirmed with unresectable HER2-negative or unknown gastric or gastroesophageal junctional adenocarcinoma treated with at least one previous chemotherapy. FGFR2 overexpression and gene amplification in the specimens were evaluated by immunohistochemical staining and fluorescence in situ hybridization methods, respectively. RESULTS: In a total of 173 eligible cases, FGFR2 immunohistochemistry score was evaluated as 0, 1, 2, 3 and 4 for 20, 80, 35, 28 and 10 cases, respectively. In 151 evaluable cases with FGFR2 immunohistochemistry scores of 1-4, FGFR2 copy number expressed as fluorescence in situ hybridization signals were detected as <4, ≥4 < 10 and ≥10 copies for 123, 16 and 12 cases, respectively. FGFR2 copy number showed an increasing tendency along with higher FGFR2 immunohistochemistry scores in the corresponding specimen. The response rate and time to treatment failure for first line chemotherapy did not have any obvious relationship to FGFR2 immunohistochemistry score and FGFR2 copy number. CONCLUSIONS: Although FGFR2 overexpression and gene amplification were shown in Japanese patients with unresectable gastric cancer, these alterations did not impact the effects of cytotoxic agents as first line chemotherapy.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

[Inflammatory reactive polyposis caused by dasatinib:a case report].

A 51-year-old man with chronic myeloid leukemia undergoing treatment with dasatinib received colonoscopy for a positive fecal occult blood test. Colonoscopy revealed more than 100 erythematous, multilobulated polyps with mucoid discharge. Endoscopic mucosal resection was performed for diagnosis, and the histological analysis of polyps showed hyperplastic glands and proliferative smooth muscle cells. Our findings suggested that the polyposis was caused by inflammation triggered due to the adverse effects associated with dasatinib. The patient discontinued dasatinib;the follow-up colonoscopy performed four months later revealed significantly improved polypoid lesions in the colon. The erythematous heads of the polyps and mucoid discharge disappeared. The cessation of dasatinib seemed to contribute to the improvement of inflammatory reactive polyposis;therefore, we inferred that the polyposis was caused by dasatinib in the present case.

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer.

BACKGROUND: S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients. METHODS: In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate. RESULTS: Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36-86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0-27.4 months), respectively (P = 0.064). Progression-free survival was significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression. CONCLUSIONS: No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.

Collagenous gastroduodenitis coexisting repeated Dieulafoy ulcer: A case report and review of collagenous gastritis and gastroduodenitis without colonic involvement.

Collagenous gastritis (CG) is a rare disorder characterized by the thick collagenous subepithelial bands associated with mucosal inflammation. There have been approximately fifty reports in the literature since it was first described in 1989. According to previous reports, CG is heterogeneous and classified into two groups-(1) cases limited to the gastric mucosa in children or young adults, and (2) CG associated with collagenous colitis in elderly adults presenting with chronic watery diarrhea. In Japan, only nine previous cases were reported, and all of them were young adults. We report a case of CG with collagenous duodenitis in a 22-year-old female. She had repeated upper gastrointestinal bleeding from a Dieulafoy lesion of the fornix, but had no symptoms of malabsorption or diarrhea. Endoscopic findings revealed striking nodularity with a smooth islet-shaped normal area in the antrum and the body. The pathological findings of nodular mucosa showed the deposition of collagen bands just under the mucoepithelial lesion. In addition, she had collagenous duodenitis in part of the bulbs, and a colonoscopy showed no abnormalities. We provide a literature review of CG and collagenous gastroduodenitis without colonic involvement.

Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer.

An open-labeled, dose-escalation phase 1 trial of Wilms tumor 1 (WT1) vaccine and gemcitabine (GEM) combination therapy for patients with advanced pancreatic cancer or biliary tract cancer was performed. The primary end point was evaluation of toxicity, safety, and optimal immunologic dose of vaccine. Human leukocyte antigen (HLA)-A 0201, HLA-A 0206, and/or HLA-A 2402-positive patients with inoperable advanced pancreatic or biliary tract cancer who had not previously been treated with GEM were eligible for this study. Six doses of GEM and 4 doses of WT1 peptide (1 or 3 mg) emulsified in Montanide adjuvant were administered over 2 months. Twenty-five patients (13 male and 12 female) were enrolled. Nine patients had inoperable advanced pancreatic cancer, 8 had gallbladder cancer, 4 had intrahepatic, and 4 had extrahepatic bile duct cancer. The adverse events were comparable to those with GEM alone. Delayed-type hypersensitivity test was positive after vaccination in 2 patients, and WT1-specific T cells in peptide-stimulated culture were detected by tetramer assay in 59% (13 of 22) of patients. The disease control rate at 2 months was 89% for pancreatic cancer and 50% for biliary tract cancer. With a median follow-up time of 259 days, the median survival time for biliary tract cancer was 288 days, and that for pancreatic cancer was 259 days. Although objective clinical efficacy was not apparent, the safety of WT1 vaccine and GEM combination therapy was confirmed in this study.

Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites.

The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer.

OBJECTIVE: Chemotherapy and immunotherapy often seem to contradict each other. However, recent reports suggested that the anticancer effects in some chemotherapeutic agents were concerned with immune response. This study was designed to evaluate the immunological reaction by gemcitabine for future clinical trial of combination therapy with gemcitabine and cancer vaccines. METHODS: We evaluated several immunological parameters in patients with advanced pancreatic cancer who received a conventional dose of gemcitabine for 2 months. Twenty-eight patients with metastasis or locally advanced tumor, including 18 gemcitabine-naïve and 10 with a history of preceding gemcitabine treatment, were enrolled in this study. The patients received gemcitabine 1000 mg/m(2) for 3 weeks, followed by 1 week of rest. We monitored the kinetics of lymphocytes, natural killer cells, monocytes, dendritic cells (DC), human leukocyte antigen (HLA)-multimer conjugated with CMV or WT1 peptide, and intracellular cytokine production of interferon-gamma and interleukin-4 by flow cytometry. The T cell receptor (TCR) repertoire was also analyzed. RESULTS: The absolute number and percentage of CD14(+) monocytes and CD11c(+) (myeloid) DC increased with gemcitabine treatment (P = 0.033 and P = 0.021). The percentage of CD123(+) (plasmacytoid) DC also increased (P = 0.034), whereas no significant change was observed in other immune parameters, including multimer, intracellular cytokine production and TCR repertoire. CONCLUSIONS: Our finding that gemcitabine treatment induced the proliferation of CD14(+) monocytes and CD11c(+) DC could support combination therapy with gemcitabine and specific immunotherapy such as peptide vaccination against pancreatic cancers.

Two cases of systemic lupus erythematosus complicated with colonic ulcers.

We report two cases of systemic lupus erythematosus (SLE) complicated with colonic ulcerations. One patient was successfully cured by steroid therapy, while the other did not respond to steroid but oral mesalazine was effective. Systemic lupus erythematosus is frequently accompanied by gastrointestinal symptoms, but colonic lesions are quite rare, and the regular treatment is not fixed yet. The high-dose steroidal regimen may be effective for microvasculitis, although it may increase the risk of perforated ulcer of the intestinal tract, which is a life-threatening complication. Further analysis of its outcomes, and establishment of the regular guideline for its treatment are expected.