Pilot study on combination of azacitidine and low-dose cytarabine for patients with refractory anemia with excess blast

This study analyzed the outcomes of the combination of azacitidine and low-dose cytarabine in patients newly diagnosed with refractory anemia with excess blast (RAEB). Patients were treated with azacitidine 75 mg/m² for 7 days subcutaneously and cytarabine 20 mg/m² intravenously for 7 days every 28 days. The assigned regimen was repeated for two cycles, then the patients treated with azacytidine alone until progression or allogeneic stem cell transplantation (allo-SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current study. After two cycles of the combination therapy, responses were achieved in nine patients (50.0%): four complete response (CR) (22.2%), one partial response (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four patients (22.2%) progressed to acute leukemia during two cycles of the combination therapy. The 1-year overall survival (OS) was 87.5% for the early response group (responses at two cycles) and 0% for the late response group (responses at four cycles, p = 0.042). Plus, the median survival time was 476 days (range, 37–718 days) for the early response group and 221 days (range, 193–249 days) for the late response group. The 1-year OS was 100% for the patients who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the combination therapy showed promising response rate when compared to treatment with azacitidine alone. However, it was limited in terms of preventing leukemic transformation. Allo-SCT would seem to be the only available treatment that can alter disease progression.     

Favorable surgical treatment outcomes for chronic constipation with features of colonic pseudo-obstruction

AIM: To determine long-term outcomes of surgical treatments for patients with constipation and features of colonic pseudo-obstruction.METHODS: Consecutive 42 patients who underwent surgery for chronic constipation within the last 13 years were prospectively collected. We identified a subgroup with colonic pseudo-obstruction (CPO) features, with dilatation of the colon proximal to the narrowed transitional zone, in contrast to typical slow-transit constipation (STC), without any dilated colonic segments. The outcomes of surgical treatments for chronic constipation with features of CPO were analyzed and compared with outcomes for STC.RESULTS: Of the 42 patients who underwent surgery for constipation, 33 patients had CPO with dilatation of the colon proximal to the narrowed transitional zone. There were 16 males and 17 females with a mean age of 51.2 ± 16.1 years. All had symptoms of chronic intestinal obstruction, including abdominal distension, pain, nausea, or vomiting, and the mean duration of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was 1.5 ± 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total colectomy, and one patient underwent diverting transverse colostomy. There was no surgery-related mortality. Postoperative histologic examination showed hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy (n = 3). Early postoperative complications developed in six patients with CPO; wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n = 1). Defecation frequencies 3 mo after surgery improved to 4.2 ± 3.2 times/d (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32 patients; all patients had improvements in constipation symptoms, but two patients needed intermittent medication for management of diarrhea. All 32 patients had distinct improvements in constipation symptoms (with a mean bowel frequency of 3.3 ± 1.3 times/d), social activities, and body mass index (20.5 kg/m² to 22.1 kg/m²) and were satisfied with the results of their surgical treatment. In comparison with nine patients who underwent colectomy for STC without colon dilatation, those in the CPO group had a lower incidence of small bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up.CONCLUSION: Chronic constipation patients with features of CPO caused by narrowed transitional zone in the left colon had favorable outcomes after total colectomy.     

Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

AIM: To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS: All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS: PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION: PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer.     

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM: To investigate the relationship between the function of vagus nerve and peptide YY_3-36 and ghrelin levels after subtotal gastrectomy.METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY_3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY_3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY_3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY_3-36.     

Predictive value of ¹⁸F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma

AIM: To investigate the correlation of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) with clinical features and the prediction of treatment response.METHODS: A total of 83 hepatocellular carcinoma (HCC) patients undergoing ¹⁸F-FDG PET before transarterial chemolipiodolization with systemic chemo-infusion between October, 2006 and May, 2009 were retrospectively enrolled. The patients included 68 men and 15 women (mean age, 60 ± 10.7 years). The effect of ¹⁸F-FDG-monitored PET uptake on clinical features and on the evaluated treatment response was ascertained with modified Response Evaluation Criteria in Solid Tumors. The PET parameters of maximal standardized uptake value of the tumor (Tsuv_max), the ratio of the tumor maximal standardized uptake value (SUV) to the liver maximal SUV (Tsuv_max/Lsuv_max) and the ratio of tumor maximal SUV to the liver mean SUV (Tsuv_max/Lsuv_mean) were tested as predictive factors.RESULTS: Among the 3 SUV parameters, the Tsuv_max/Lsuv_mean ratio (cutoff value of 1.90) was significantly associated with tumor burden including tumor size, tumor number, α-fetoprotein levels and tumor stage (P < 0.001, P = 0.008, P = 0.011, P < 0.001, respectively). The objective response rates in patients with a high SUV ratio (≥ 1.90) were significantly better than those with a low SUV ratio (< 1.90) (P = 0.020). The overall survival rates of patients exhibiting a low Tsuv_max/Lsuv_mean ratio (< 1.90) and those with a high SUV ratio (≥ 1.90) was 38.2 and 10.3 mo, respectively (P < 0.01). However, the time to progression showed no significant difference between the groups (P = 0.15).CONCLUSION: ¹⁸F-FDG PET can be an important predictor of HCC treatment. In particular, the Tsuv_max/Lsuv_mean ratio (cutoff value of 1.90) can provide useful information in treatment prognosis for HCC patients treated with locoregional therapy.     

Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis

Hepatic artery pseudoaneurysm (HAP) is a very rare disease but in cases of complication, there is a very high mortality. The most common cause of HAP is iatrogenic trauma such as liver biopsy, transhepatic biliary drainage, cholecystectomy and hepatectomy. HAP may also occur with complications such as infections or inflammation associated with septic emboli. HAP has been reported rarely in patients with acute pancreatitis. As far as we are aware, there is no report of a case caused by acute idiopathic pancreatitis, particularly. We report a case of HAP caused by acute idiopathic pancreatitis which developed in a 61-year-old woman. The woman initially presented with acute pancreatitis due to unknown cause. After conservative management, her symptoms seemed to have improved. But eight days after admission, abdominal pain abruptly became worse again. Abdominal computed tomography (CT) was rechecked and it detected a new HAP that was not seen in a previous abdominal CT. Endoscopic retrograde cholangiopancreatography (ERCP) was performed because of a suspicion of hemobilia as a cause of aggravated abdominal pain. ERCP confirmed hemobilia by observing fresh blood clots at the opening of the ampulla and several filling defects in the distal common bile duct on cholangiogram. Without any particular treatment such as embolization or surgical ligation, HAP thrombosed spontaneously. Three months after discharge, abdominal CT demonstrated that HAP in the left lateral segment had disappeared.     

Respecting Symptoms in Thoracic Aortic Aneurysm Management: A Case of Symptomatic Necrotizing Granulomatous Aortitis

A 41-year-old woman presented with chest pain of unclear etiology in the setting of a mildly dilated ascending aorta. Computed tomography angiography showed an aorta with an irregular contour and an aneurysm of 4.5 cm. There was no radiographic evidence of rupture or dissection. The patient was taken to the operating room and was found to have severe aortitis with marked localized wall thinning at imminent risk of aortic rupture. Aortic pathology demonstrated necrotizing granulomas of noninfectious etiology. This case illustrates the importance of respecting symptoms in surgical decision making for thoracic aortic aneurysms that may not meet standard interventional criteria.