Virological response for recurrent hepatitis C improves long‐term survival in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV‐related end‐stage liver disease. We conducted this large, single‐center, retrospective study to ascertain the long‐term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon‐based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty‐six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV‐RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV‐RNA) 39.6% (97/245). The median follow‐up after completion of antiviral treatment was 2081 days. Using Kaplan–Meier method, patients who achieved SVR were shown to have significantly better 5‐year patient survival (95.2%) than the NR group (49.9%) (P < 0.001), and a trend toward better 5‐year survival than relapsers (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group (P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long‐term patient outcomes in patients transplanted for hepatitis C.     

SPan-1 Is a Useful Prognostic Marker for Patients with Stage IV Gastric Cancer Who Underwent Palliative Gastrectomy: A Retrospective Multivariate Study

Background

We retrospectively investigated prognostic factors to be used in selecting the patients with stage IV gastric cancer (GC) who have an unfavorable prognosis after palliative gastrectomy.

Methods

A total of 146 GC patients at stage IV who had undergone palliative gastrectomy were enrolled. Various clinicopathological parameters were evaluated for prognosis.

Results

Surgical morbidity and hospital mortality occurred in 35 (23.9 %) and 4 (2.7 %) patients, respectively. The overall 5-year survival rate and the median survival time were 11.2 % and 13.2 months, respectively. Of the 146 patients, 64 had uncomfortable symptoms associated with GC and 76 had no such symptoms. Of the 64 patients with uncomfortable symptoms, 60 (93.7 %) experienced relief of these symptoms after palliative surgery. Multivariate analysis for patients without uncomfortable symptoms associated with GC revealed that the number of incurable factors and serum SPan-1 level were independent prognostic factors.

Conclusions

Patients with stage IV GC who had multiple incurable factors and a high level of serum SPan-1 might not be candidates for palliative gastrectomy for the purpose of prognostic benefit.     

Chronic encapsulated expanding hematoma in nonfunctioning pituitary adenoma

The diagnosis and treatment of pituitary macroadenomas with entire hematoma fluid accumulation are problematic. Such lesions are often difficult to completely resect, and recurrence is not uncommon. We present five cases of pituitary macroadenomas entirely composed of hematoma fluid and investigated their histopathology to clarify the mechanism of the hematoma fluid accumulation. Five patients with pituitary adenoma and significant intra-tumor hematoma underwent transsphenoidal resection and were retrospectively reviewed for their clinical status, findings on magnetic resonance imaging (MRI), intraoperative findings, and histopathology. The specific surgical techniques used to address these cases were also reviewed. All patients were diagnosed with nonfunctioning pituitary adenomas by histopathological examination. MRI showed all tumors extended to the cavernous sinus. Histopathology showed tumor tissues were located between the thick granulation tissue and the pseudocapsule of the tumor. The thick granulation tissues were composed of collagenous layers, neovascular vessels, and necrotic red blood cells, indicating repeat hemorrhage from the granulation tissues. The boundary between adenoma and normal pituitary gland was identified during surgical removal in four patients and was not identified in the other patient who showed a recurrence 2 years later. Clinical and histopathological findings indicate hematoma fluid accumulation in the present cases is caused by repeat hemorrhage from the reactive granulation tissues and can be regarded as a chronic encapsulated expanding hematoma. In these cases, the boundary between adenoma and normal pituitary gland should be identified before puncturing the hematoma fluid to minimize the risk of tumor recurrence.     

Treatment When Prognostic Factors Do Not Match St. Gallen Recommendations: Profiling of Prognostic Factors among HR(+) and HER2(−) Breast Cancer Patients

Background

The St. Gallen consensus provides treatment recommendations for breast cancer based on prognostic factors. Although many patients’ prognostic patterns are not easily matched with the prognostic patterns listed in the St. Gallen consensus, there has been no systematic investigation reporting the gap between treatment recommendations and actual postoperative treatment choices in clinical practice.

Methods

Four hundred seventy-one patients with hormone receptor-positive [HR(+)] and human epidermal growth factor receptor type 2-negative [HER2(?)] breast cancer were analyzed. These patients were classified into either the “crisp treatment group” or “fuzzy treatment group” based on the definitiveness of postoperative treatment selection based on St. Gallen treatment recommendations. The patients in the fuzzy treatment group were further classified into strata in which patients within each stratum shared the same prognostic factor patterns with similar recurrence rates.

Results

A total of 87.3 % of HR(+)HER2(?) patients were designated to the fuzzy treatment group. Four prognostic strata were constructed according to the survival tree model, and revealed that patients with poor prognostic profiles tended to receive endocrine therapy with chemotherapy. This suggests that postoperative chemotherapy is useful, although there was no statistical significance.

Conclusions

We constructed prognostic profiles of patients in the fuzzy treatment group and examined the recurrence rates associated with two treatment regimens within each prognostic profile. These findings are exploratory, but they may be useful for planning prospective studies of the effectiveness of postoperative treatment regimens among patients with a heterogeneous combination of prognostic factors.     

The mitochondrial protein frataxin is downregulated in hemodialysis patients

Background

The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD).

Methods

Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting.

Results

The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α.

Conclusion

The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.