Two-stage hepatectomy for multiple bilobular liver metastases from colorectal cancer

BACKGROUND/AIMS: To determine an appropriate surgical treatment for patients with multiple liver metastases, we evaluated the efficacy of two-stage hepatectomy in patients with multiple bilobular liver metastases from colorectal carcinoma. METHODOLOGY: Some patients with multiple liver metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. Two-stage hepatectomy was performed in 11 patients. RESULTS: Two-stage hepatectomy was feasible in all of the 11 patients. In 3 of them, the first stage was a major resection (more extensive than a lobectomy). This first hepatectomy was uneventful in all patients. The second hepatectomy was also uneventful in nine patients, but in one of the other two, a perihepatic fluid infection occurred, and in the other, postoperative liver failure developed due to a right subphrenic abscess. However, all patients were discharged. The percentage of the expected resection volume at one time, calculated from CT volumetry, was 75.5+/-1.2% and the prognostic score as surgical risk was 56.6+/-4.5. In two-stage hepatectomy cases, the percentage of the resected volume and the prognostic score in the first hepatectomy were 25.4+/-6.4% and 6.7+/-7.3, and in the second, 45.7+/-4.5% and 28.5+/-5.8. During the follow-up procedures, a residual hepatic recurrence was observed in 6 patients, and pulmonary recurrence in 9. The 1- and 3-year survival rates after the first hepatectomy were 90% and 45%, with median survivals of 18 months from the first hepatectomy. CONCLUSIONS: Two-stage hepatectomy is a surgical modality intended for patients with initial unresectable metastases. However, following such surgery, protective treatment against residual liver recurrence and lung metastasis will be a most important issue.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.     

Relative contributions of cardiorespiratory fitness and visceral fat to metabolic syndrome in patients with diabetes mellitus

The objective of this study was to examine the contribution of endurance fitness and visceral fat accumulation on the prevalence of metabolic syndrome in Japanese male patients with either an impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM). The subjects of this cross-sectional study consisted of 135 Japanese male patients with either IGT or type 2 DM who had not taken any medication or intervention. They were classified into three fitness categories (low, moderate, and high) based on the tertiles of their maximal oxygen uptake ( [Formula: see text] O(2)max) predicted by the Astrand nomogram using a cycle ergometer. Metabolic syndrome was defined based on the WHO criteria. The visceral fat area (VFA) was determined using a computed tomography scan. The age- and VFA-adjusted odds ratio was 3.49 (95% CI, 1.13-10.82) for subjects in the low fitness category in comparison to those in the high fitness category. We calculated the odds ratio for the prevalence of metabolic syndrome in the nine categories classified based on the three VFA and three [Formula: see text] (2)max levels. In Moderate- and Low- [Formula: see text] (2) max categories, the odds ratios increased in line with increases in the VFA level. The highest odds ratios were observed in the low fitness and high visceral fat group. In the High- [Formula: see text] O(2)max category, no significant odds ratios were observed in the Moderate- and High-VFA categories. These results indicate that a high degree of cardiorespiratory fitness positively contributed to the low prevalence of metabolic syndrome in Japanese male patients with IGT and type 2 DM.     

Effect of L-dopa in young patients with hypertension

The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.     

Levels of Rheumatoid Factor Isotypes, Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinase-1 in Synovial Fluid from Various Arthritides

When synovial effusion is the only symptom, it is often difficult to make an exact diagnosis of the arthritic disease. To distinguish various types of arthritis with synovial effusion, we measured the levels of matrix metalloproteinase-3 (MMP-3, Stromelysin), tissue inhibitor of metalloproteinase-1 (TIMP-1) and rheumatoid factor (RF) isotypes in synovial fluid (SF) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), pyogenic arthritis (PA), pseudogouty arthritis (PG), gouty arthritis (GA) and traumatic arthritis (TA). SF was aspirated from the knee joint or the ankle joint. Levels of IgG-, IgM- and IgA-RF isotypes were measured by ELISA. Levels of MMP-3 and TIMP-1 in SF were simultaneously determined by a one-step EIA system. Levels of IgG-RF, IgM-RF and MMP-3 in SF from RA patients were significantly higher than those in OA, PA, PG, GA and TA. However, IgA-RF in SF from RA patients, when compared with PA and GA, did not show a significantly increased level. In addition, TIMP-1 in SF from RA, when compared with PA and TA, also has not shown a significantly increased level. Therefore, in addition to analysing clinical data, measurements of IgG-RF, IgM-RF and MMP-3 in SF may contribute in distinguishing RA from other arthritic diseases. Received: 18 January 1999 / Accepted: 15 June 1999     

Cardiac free wall rupture in acute myocardial infarction: ameliorative effect of coronary reperfusion.

To investigate the pathophysiology of cardiac free wall rupture (cardiac rupture) following acute myocardial infarction (AMI), and to clarify whether reperfusion therapy prevents cardiac rupture, 1,329 cases of AMI (conventional therapy group: 807 cases and reperfusion therapy group: 533 cases) were studied retrospectively. The overall incidence of cardiac rupture was 2.3% (2.7% in the conventional therapy group vs. 1.7% in the reperfusion therapy group). Patients with cardiac rupture were divided into two subgroups according to the time interval from the onset of AMI to cardiac rupture (early rupture less than or equal to 72 h and late rupture greater than or equal to 4 days). The indices of initial evolution of AMI was a significant risk of early cardiac rupture. The reperfusion therapy group showed significantly lower incidence of late rupture (0.4 vs. 1.5% in conventional therapy group; p less than 0.05). The incidence of cardiac rupture in the unsuccessful reperfusion therapy group was higher than that of the successful group (5.9% of 118 cases vs. 0.5% of 404 cases; p less than 0.05). It is concluded that the etiology of cardiac rupture following AMI cannot be explained by any single factor. Early rupture depends on the initial evolution of AMI, and early reperfusion and collateral flow prevent the late onset cardiac rupture.     

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis

Purpose

Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO₂) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF.

Methods

We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO₂ and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation.

Results

Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO₂ during sleep and total sleep time spent with SpO₂?<?90% were associated with the sustained pattern, and apnea–hypopnea index was associated with the intermittent pattern.

Conclusion

We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

     

New chemotherapy for patients with advanced hepatocellular carcinoma: Pilot study of β-interferon and doxorubicin one-shot intra-arterial chemotherapy

Background: Patients with advanced hepatocellular carcinoma (HCC) need an effective treatment modality because of the poor prognosis of the disease. From an in vitro study, beta-interferon (IFN-beta) has been reported to enhance the antiproliferative effects of doxorubicin on HCC cell lines. In the present study, we investigated the therapeutic effects of combined IFN-beta and doxorubicin intra-arterial injection therapy on patients with advanced HCC. Methods: IFN-beta (3 MIU) and doxorubicin (10 mg/bodyweight) were given by one-shot intra-arterial injection through an arterial port to patients with advanced HCC. One treatment course consisted of three intra-arterial injections per week for 4 weeks. Three courses were conducted and evaluation was done monthly. Results: Eleven patients with advanced HCC were treated with combined IFN-beta and doxorubicin. One patient enteredcomplete remission (CR), seven patients were evaluated as having stable disease (SD) and three as having progressive disease (PD). The mean overall survival was 10 months. The mean survival for CR and SD patients was 15 months, and that for PD patients was 6 months (P = 0.0464, log-rank test). Decrease of serum total bilirubin was observed for all patients. Conclusion: Combined IFN-beta and doxorubicin intra-arterial therapy offers an effective chemotherapy option for patients with advanced HCC by improving liver function and having tolerable side-effects.     

An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice

The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept.