Atypical Splenic Abscesses Due to Clostridioides difficile.

BACKGROUND Splenic abscess is a rare infectious disease that occurs after bloodstream infection and trauma. It has become more common due to an increase in the number of immunocompromised patients. They typically present with round cystic lesions demonstrated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Clostridioides difficile (formerly Clostridium difficile) is a well-known cause of pseudomembranous colitis, but extraintestinal manifestations are very rare. To the best of our knowledge, only 9 cases of splenic abscess due to C. difficile have been reported in the literature. CASE REPORT A 90-year-old man presented with weight loss, fever, and abdominal pain. Contrast-enhanced CT revealed splenomegaly with irregular hypodense nodules. Image-guided biopsy or drainage was not performed for a technical reason. MRI showed atypical nodules with mixed high and low signals on both T1- and T2-weighted images, which were inconclusive. A laparoscopic splenectomy was performed, which resulted in partial removal due to severe adhesion of the spleen to the surrounding tissues. Cultures of splenic pus yielded C. difficile, Enterococcus faecium, and Bacteroides fragilis. Pathological examination of the spleen showed widespread abscesses with hemorrhage and necrosis, leading to the diagnosis of splenic abscesses. Intravenous administration of vancomycin, clindamycin or metronidazole was ineffective. He died of fatal arrhythmia 5 months after the initial diagnosis of splenic abscess. CONCLUSIONS Splenic abscess can present with atypical imaging findings owing to chronic inflammation, bleeding, and necrosis. Although polymicrobial, this is the tenth reported case of splenic abscess caused by C. difficile.

Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases.

BACKGROUND: Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study. METHODS: After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery. RESULTS: Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001). CONCLUSION: Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival.

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.

BACKGROUND: The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV). METHODS: In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS). RESULTS: Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15-9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38-0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48-1.35; P = 0.409). CONCLUSION: Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000013.

[A Case of Effective Whole-Brain Irradiation and Lapatinib/Capecitabine Combination Therapy for HER2-Positive Breast Cancer with Multiple Brain Metastases].

We report the case of a 48-year-old female patient with HER2-positive and hormone receptor-negative breast cancer with multiple liver metastases. She underwent 6 cycles of FEC followed by docetaxel plus trastuzumab (TZB), resulting in a clinical complete response. After 15 cycles of a TZB-containing regimen, she complained of dizziness and nausea, and imaging examinations revealed multiple brain metastases. Whole-brain irradiation(33.6 Gy) was performed, and the chemotherapy regimen was changed to lapatinib (LAP: orally at 1,250 mg/day, every day) and capecitabine (CAP: orally at 2,000 mg/m2, every day for 2 weeks, followed by a 1-week rest interval, as 1 cycle). After 6 weeks of the new treatment, magnetic resonance imaging revealed marked shrinkage of brain metastases. A clinical complete response was maintained for 19 months. While brain metastasis is an important problem with treatment with TZB, LAP is drawing attention because of its ability to pass the blood-brain barrier because of its small molecular weight. LAP/CAP combination therapy may be an effective treatment option for brain metastases of HER2-positive breast cancer in which TZB essentially has no effect.

A combination of oral uracil-tegafur plus leucovorin (UFT + LV) is a safe regimen for adjuvant chemotherapy after hepatectomy in patients with colorectal cancer: safety report of the UFT/LV study.

The use of adjuvant systemic chemotherapy for resectable liver metastases from colorectal cancer (CRC) is controversial because no trial demonstrated its benefit. We conducted the phase III trial to evaluate UFT/leucovorin (LV) for colorectal liver metastases (CRLM). The primary endpoint has not been available until 2014, we first report the feasibility and safety data of UFT/LV arm. In this multicenter trial, patients who underwent curative resection of liver metastases from colorectal cancer were randomly assigned to receive surgery alone or surgery followed by adjuvant chemotherapy with UFT/LV. The primary endpoint was relapse-free survival. Secondary endpoints included overall survival and safety. A total of 180 patients were enrolled, 90 were randomly assigned to receive UFT/LV therapy. Eighty two of whom were included in safety analyses. In the UFT/LV group, the completion rate of UFT/LV was 54.9%, the relative dose intensity was 70.8% and grade 3 or higher adverse events occurred in 12.2% of the patients. Elevated bilirubin levels, decreased hemoglobin levels, elevated alanine aminotransferase levels, diarrhea, anorexia were common. Most other adverse events were grade 2 or lower and tolerable. In conclusions, UFT/LV is a safe regimen for postoperative adjuvant chemotherapy in patients who have undergone resection of liver metastases from colorectal cancer. Further studies are warranted to improve completion rate, but UFT/LV is found to be a promising treatment in this setting.

Resection of a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn's disease under infliximab treatment: a case report.

INTRODUCTION: A liver abscess in Crohn's disease is a rare but important entity that is associated with a poor prognosis and high mortality when treatment is delayed. We report a case of successful liver segmentectomy for a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn's disease under infliximab treatment. CASE PRESENTATION: A 31-year-old Japanese man, who had been treated with infliximab infusions for Crohn's disease, was referred to our hospital presenting with an abrupt onset of high fever and an elevated white blood cell count and serum C-reactive protein level. Computed tomography revealed a liver abscess occupying segment 8. The limited effect of percutaneous transhepatic abscess drainage and antibiotics led us to perform radical resection of the abscess. The patient recovered quickly after surgery and the postoperative course was uneventful. CONCLUSION: The present case suggests that surgical removal of an abscess should be considered for patients under immunosuppression or refractory to conventional treatment.

A rapidly progressive and fatal case of nonalcoholic steatohepatitis following pancreaticoduodenectomy.

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) usually occurs in patients with metabolic syndrome. However, it can develop in relation with pancreaticoduodenectomy (PD) independent of insulin resistance. NAFLD/NASH potentially progresses to liver cirrhosis and subsequent end-stage liver disease, but in general the disease progression is very slow. We here report the case of a 57-year-old Japanese woman who underwent PD for pancreatic head cancer, subsequent to which she developed rapidly progressive NASH without prior liver diseases, resulting in death due to hepatic failure 5 months after PD. Marked body weight loss was a distinguishing clinical feature. Severe malnutrition induced by pancreatic exocrine insufficiency, postoperative eating disorder and exacerbation of diabetes mellitus were thought to be etiologically associated with the rapid progression of her disease. This case suggests the necessity of close hepatic surveillance as well as nutritional evaluation followed by prophylactic pancreatic enzyme replacement and nutritional supply after PD.

Application of fluorescent cholangiography to single-incision laparoscopic cholecystectomy.

BACKGROUND: Although the use of single-incision laparoscopic cholecystectomy (SILC) is spreading rapidly, this technique has disadvantages. It does not allow for sufficient surgical views to be obtained or for intraoperative radiographic cholangiography to be performed. Fluorescent cholangiography using a preoperative intravenous injection of indocyanine green (ICG) may be useful for identifying the biliary tract during both SILC and conventional laparoscopic cholecystectomy. METHODS: For seven patients undergoing SILC, 1 ml of ICG (2.5 mg) was administered by intravenous injection before the surgery. The prototype fluorescent imaging system consisted of a xenon light source and a 30° laparoscope (diameter, 10 mm) equipped with a charge-coupled device camera capable of filtering out light with wavelengths shorter than 810 nm. The laparoscope was introduced through an umbilical trocar. Fluorescent cholangiography then was performed by changing the color images to fluorescent images using a foot switch during dissection of the triangle of Calot. RESULTS: Fluorescent cholangiography identified the confluence between the cystic duct and the common hepatic duct in all seven patients before and throughout the dissection of the triangle of Calot. The interval from the injection of ICG to the first obtained fluorescent cholangiography before dissection of the triangle of Calot ranged from 35 to 75 min. CONCLUSIONS: Fluorescent cholangiography enabled real-time identification of the extrahepatic bile ducts during SILC without necessitating catheterization of the bile duct. Such properties of fluorescent cholangiography are expected to be helpful for ensuring the safety of SILC and expanding the indications for the procedure.

Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease.

IgG4-related disease is a recently recognized fibroinflammatory disorder characterized by extensive IgG4-positive plasma cell and lymphocyte infiltration of various organs. The pancreatic manifestation of IgG4-related disease is called autoimmune pancreatitis (AIP), in which autoimmune mechanisms are likely involved. On the other hand, some autoimmune and chronic inflammatory disorders, such as Sjögren's syndrome and rheumatoid arthritis, are associated with increased risks of non-Hodgkin lymphoma (NHL). There have been a few reports of cases with IgG4-related disease that had subsequently developed NHL, however, all of them suffered from B-cell lymphoma. We describe the first case of NHL, compatible with a subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which arose in IgG4-related sclerosing cholangitis. As patients with IgG4-related disease may be at an increased risk of developing NHL, such presentation during the follow-up of IgG4-related disease should be carefully scrutinized to exclude NHL.

Inclusion of tumor markers improves the correlation of the Milan criteria with vascular invasion and tumor cell differentiation in patients with hepatocellular carcinoma undergoing liver resection (#JGSU-D-07-00462).

The currently used criteria, such as the Milan criteria, to select a candidate of liver transplantation for HCC consists of size and number of tumors because vascular invasion and poor differentiation, the strongest prognostic factors, are difficult to be assessed preoperatively. We hypothesized that inclusion of two tumor markers (alpha-fetoprotein and des-gamma-carboxy prothrombin) into the criteria would increase the prediction accuracy of these factors. Our hypothesis was tested in 478 HCC patients undergoing liver resection. The models with or without markers, constructed at predicting vascular invasion (n=150) or poor differentiation (n=49), were compared. The model including markers was superior at predicting the absence of vascular invasion to either the Milan criteria alone [at 81.2% sensitivity; specificity, 52.4 vs 43.3%; difference, 9.1%(95% CI, 1.3-14.2%)] or a model in which size and number varied freely [AUCs of receiver operating characteristic curves, 75.2 vs 69.1%; difference, 6.1%(2.33-10.7%)]. The model incorporating markers was also superior at predicting well to moderate differentiation to either the Milan criteria [at 74.5% sensitivity; specificity, 57.1 vs 38.8%; difference, 18.3%(2.4-32.7%)] or a model with size and number [AUCs, 71.5 vs 59.0%; difference, 12.5%(5.84-21.4%)]. In conclusion, the tumor marker levels should be considered when selecting patients with HCC for liver transplantation.

Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.

Effect of apolipoprotein E polymorphism on bile lipid composition and the formation of cholesterol gallstone.

OBJECTIVE: It remains a matter of controversy whether possession of the apolipoprotein E4 (apoE4) allele is a genetic risk factor for the formation of cholesterol gallstones. The aim of the present study was to test this hypothesis by investigating the effect of apoE4 on bile lipid composition in normal subjects and in patients with cholesterol gallstones and to evaluate the distributions of apoE alleles in these two groups. METHODS: The study population consisted of 79 patients who underwent open or laparoscopic cholecystectomy for symptomatic cholesterol gallstone disease. The control group (n = 53) included 11 patients with benign gallbladder polyps and 42 normal subjects acting as donors in living donor liver transplantation. The apoE genotypes were assessed by dot blot hybridization with digoxigenin-labeled probes. Bile lipid composition was determined by enzymatic assays and high performance liquid chromatography. RESULTS: Bile lipid composition and cholesterol saturation index (CSI) were similar in the control subjects harboring the apoE4 allele and those without apoE4 (mean CSI, 85.9% and 72.2%, respectively, p = 0.69). Likewise, in the cholesterol gallstone patients, bile lipid composition and CSI were similar in the patients with and without apoE4 allele (mean CSI, 134.9% vs 152.2%, p = 0.6). Furthermore, the prevalence of the apoE4 allele was similar in the patients with cholesterol gallstones and in the control group (8.5% vs 7.6%, p = 0.46, OR = 0.88; 95% CI = 0.64-1.22). CONCLUSIONS: The apoE4 allele is not a contributory factor to cholesterol gallstone formation, at least in the Japanese population.

alpha-Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: a prospective study.

alpha-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC. Peripheral blood samples were taken from 87 patients before and after surgery to determine the presence of AFP mRNA by use of a reverse-transcription polymerase chain reaction. A primary endpoint was recurrence-free interval. AFP mRNA was detectable preoperatively in 31 patients (36%) and postoperatively in 30 patients (34%). With a median follow-up period of 28 months (range, 3-41 months), HCC recurred in 46 patients (53%). Among 4 groups separated according to preoperative and postoperative AFP mRNA status, patients with consistent positivity of AFP mRNA showed the highest recurrence rate (85%) and trend to distant or multiple recurrence. The recurrence-free interval was significantly shorter in patients with postoperative positivity of AFP mRNA than in those without (53% [95% CI, 36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60% [95% CI, 46-75] at 2 years; P =.014), whereas the preoperative positivity of AFP mRNA provided no significance (P =.100). Cox's proportional-hazards model identified the postoperative positivity of AFP mRNA as an independent prognostic factor for HCC recurrence (relative risk, 2.33; 95% CI, 1.26-4.34; P =.007). In conclusion, postsurgical recurrence of HCC can be predicted by detecting AFP mRNA-expressing cells in peripheral blood.