Long-term functional changes after low anterior resection for rectal cancer compared between a colonic J-pouch and a straight anastomosis

BACKGROUND/AIMS: We prospectively compared changes in function between colonic J-pouch and straight anastomoses from 1 to 5 years after low anterior resection for rectal cancer. METHODOLOGY: At 1, 3, and 5 years after surgery, functional outcome was compared between 48 patients with J-pouch reconstruction (J group) and 51 with straight anastomosis (S group), using a 17-item questionnaire (overall best, 0; overall worst, 26). Reservoir function was evaluated manovolumetrically. RESULTS: At 5 years, patients with ultralow anastomoses (< or =4 cm from anal verge) had fewer bowel movements during day or night, and less urgency and soiling in the J than S group. At that time, patients with low anastomoses (5 to 8 cm above the verge), had fewer bowel movements at night and less urgency in the J than S group. Manovolumetric results were better in the J than S group for both anastomotic levels. Functional scores improved significantly over time for both anastomotic levels, especially in the S group. Mean scores with ultralow anastomoses were J-group, 5.6 at 1 year vs. 5.3 at 3 years (P = 0.0304) vs. 3.7 at 5 years (P < 0.0001); and S group, 10.2 at 1 year vs. 9.6 at 3 years (P = 0.0063) vs. 7.3 at 5 years (P < 0.0001). Mean scores with low anastomoses were J group, 3.4 at 1 year vs. 3.1 at 3 years (P = 0.0052) vs. 2.1 at 5 years (P = 0.0003); and S group, 5.2 at 1 year vs. 3.8 at 3 years (P < 0.0001) vs. 2.7 at 5 years (P < 0.0001). Manovolumetric results improved overtime in both groups. CONCLUSIONS: Functional outcome improved in the J and especially the S group over 5 years. However, function was better in the J than S group at all time points.     

Liver metastases with massive portal venous tumor thrombi from colorectal cancer: can be treated by surgical resection?

BACKGROUND/AIMS: The surgical treatments for liver metastases from colorectal cancer with massive portal venous tumor thrombi were evaluated. METHODOLOGY: Five patients, among the 142 patients who underwent hepatic resection for liver metastases from colorectal cancer from 1989 to 1998, were included in this study. The tumor thrombi in the main portal vein were removed by the following procedures; (1) the circumferential incision of the first branch of the portal vein and removal of the exposed tumor thrombi with ring forceps and suction, (2) temporary clamping of the distal end, (3) dilatation of the round ligament and the venous cannula was inserted into the umbilical portion, (4) washing out of the residual tumor thrombi, (5) declamping of the distal end and closing suture of the cut end of the portal branch. RESULTS: All patients had metachronous metastases and underwent resections of the primary tumor within 2 years. The surgical procedures performed were as follows: two cases that underwent right hepatectomies with portal venous tumor thrombectomies, one right trisectionectomy with portal venous tumor thrombectomy, one right hepatectomy plus limited resection of the contralateral lobe, and one left lateral sectionectomy with limited resection of the right lobe. All patients had no major postoperative complications and returned to their social lives within 1 month after operation. The intra-arterial catheter devices were implanted in four patients in order to receive adjuvant chemotherapy. One patient survived the 36-month period after liver resection, although 4 patients died of liver recurrence within 12 months. The mean survival time was 14.4 months and the overall 1-year survival rate was 20.0 percent. CONCLUSIONS: Surgical resection for this disease may bring longer survival rates for some patients, but not be an effective therapeutic option in our series. We should create other adjuvant therapies to improve these survival rates.     

gamma-Glutamyltransferase predicts cardiovascular death among Japanese women

The clinical importance of gamma-glutamyltransferase (GGT) has recently been debated. Although some studies have suggested that the relationship between GGT and cardiovascular disease (CVD) mortality is independent of alcohol consumption, to our knowledge no studies have reported the relationship between GGT and CVD mortality in never-drinker subgroups. Since Japanese women are known to have a lower prevalence of alcohol consumption, we examined whether GGT predicts CVD mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82 CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive relationship was unchanged in the never-drinkers subgroup (HR for log-transformed continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were observed in men. GGT displays a strong positive association with CVD mortality among Japanese women, for whom the prevalence of ever-drinkers is very low. Exploring the significance and biological mechanisms of GGT might provide useful insights into CVD prevention.     

Comparative study of culture conditions for maintaining CYP3A4 and ATP-binding cassette transporters activity in primary cultured human hepatocytes

The aim of this study was to determine suitable culture conditions for maintaining the activity of cytochrome p450 (CYP) 3A4 and drug transporters in primary cultured human hepatocytes. Human hepatocytes were isolated using the two-step collagenase perfusion technique and were cultured with four different media, serum-free William's E medium (serum-free WEM), WEM containing fetal calf serum (FCS-WEM), WEM with human serum (HS-WEM), and Lanford's medium. The albumin levels were maintained for 7 days in hepatocytes. Although CYP3A4 mRNA levels gradually decreased from 3 days, CYP3A4 and hepatocyte nuclear factor-4α alpha protein levels and activities were maintained for 7 days in hepatocytes cultured with serum-free WEM and Lanford's but not in those with FCS-WEM and HS-WEM. Furthermore, CYP3A4 protein levels were significantly increased by the addition of rifampicin and dexamethasone to the culture media, indicating that the induction potential was maintained. The protein levels of P-glycoprotein, multi-drug-resistance-2, and breast cancer-resistance protein were maintained for 7 days in all media. Serum-free WEM and Lanford's also maintained protein levels of CYP2C19, CYP2D6, and organic anion transporter polypeptide in the hepatocytes. Serum-free WEM and Lanford's may be appropriate culture media for maintaining CYP3A4 and drug transporter protein levels in primary cultured hepatocytes.     

The frontal cortex is activated during learning of endoscopic procedures

Background

To date, several training and evaluation systems for endoscopic surgery have been developed, such as virtual-reality simulators and box trainers. However, despite current advances in these objective assessments, no functional brain studies during learning of endoscopic surgical skills have been carried out. In the present study, we investigated cortical activation using near-infrared spectroscopy (NIRS) during endoscopic surgical tasks.

Study design

A total of 21 right-handed subjects, comprising 4 surgical experts, 4 trainees, and 13 novices, participated in the study. Suturing and knot-tying tasks were performed in a box trainer. Cortical activation was assessed in all subjects by task-related changes in hemoglobin (Hb) oxygenation using NIRS.

Results

In surgical experts and novices with no experience of endoscopic surgical training, we found no changes in oxy-Hb, deoxy-Hb or total-Hb levels in any of the frontal channels. In surgical trainees and one novice with experience of endoscopic surgical training, we found significant increases in oxy-Hb and total-Hb levels in most of the frontal channels. There were significant differences in oxy-Hb and total-Hb levels in CH-19 between surgical experts and trainees (p = 0.02 for both), and between surgical trainees and novices with no experience of endoscopic surgical training (p = 0.008 for both). Furthermore, additional training increased oxy-Hb levels in the frontal cortex of novices with no experience of endoscopic surgical training but had no such effect on surgical experts.

Conclusions

The present data suggest that NIRS is a feasible tool for assessing brain activation during endoscopic surgical tasks, and may have a large impact on the future development of teaching, training, and assessment methods for endoscopic surgical skills.     

Evaluation of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia with persistent symptoms following treatment with alpha1-adrenoceptor blocker

We examined the effectiveness of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia (BPH) whose lower urinary tract symptoms (LUTS) caused by BPH were not adequately relieved by an alpha1-adrenoceptor blocker. Twenty-nine patients with insufficient improvement in the International Prostate Symptom Score (IPSS) and quality of life (QOL) score after administration of 50 mg naftopidil for 4 weeks or more received 6 tablets of Eviprostat in addition to naftopidil for another 2 weeks or more. With supplemental administration of Eviprostat, significant improvement was observed in the symptoms of incomplete emptying, daytime frequency, intermittency, weak stream, total IPSS, sum of the IPSS subscores for voiding symptoms (intermittency, weak stream and straining), sum of the IPSS subscores for storage symptoms (daytime frequency, urgency and nocturia), and QOL score. Supplemental administration of Eviprostat is therefore effective for the improvement of LUTS and QOL in BPH patients resistant to an alpha1-adrenoceptor blocker.     

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer

Background

Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent.

Methods

Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage.

Results

A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev.

Conclusions

This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.

     

Effect of conventional risk factors for excess cardiovascular death in men: NIPPON DATA80.

BACKGROUND: The present study examined how sex differences in conventional risk factors for cardiovascular disease (CVD), especially smoking, account for excess male mortality from CVD in Japan. METHODS AND RESULTS: In a 14-year follow-up study, causes of death were ascertained among 10,546 Japanese aged 30 years or older at the baseline. The proportion of the excess male risk of CVD explained by the differences in risk factors was estimated as (HR0-HR1)/(HR0-1), where HR0 is the age-adjusted hazard ratio (men vs women) and HR1 is the age and risk factor-adjusted hazard ratio. The age-adjusted male:female ratios were 1.60 (95% confidence interval (CI), 1.32-1.94) for CVD, 1.75 (95% CI, 1.33-2.30) for stroke, and 1.55 (95% CI, 0.97-2.49) for coronary heart disease. The proportion of excess male risk of CVD explained by smoking was 46% and excess risk explained by all risk factors including smoking was 36%. In men, drinking habits decreased the excess risk of CVD. Except for the association between drinking habits and CVD, the impact of the hazard ratios of conventional risk factors had no sex difference. CONCLUSIONS: Smoking contributes substantially to excess male mortality from CVD when the smoking rates vary substantially by sex.     

Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors.

Recently, the stromal invasion grading system was proposed for small adenocarcinomas of < or =2.0 cm. The system is based on the presence or absence of a fibrotic focus, and the extent of invasion into the fibrotic focus. Although stromal invasion grading system closely correlated with the prognosis, stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors and showed variable prognosis. In this study, we investigated whether stromal invasion grading system could be applied to and validated in pT1 adenocarcinomas as the TNM classification is the most universally used system. Furthermore, we investigated whether stromal invasion grade 3 cases could be subclassified according to the presence and absence of micropapillary pattern. The study included 120 cases of pT1 lung adenocarcinomas, of which 81 (68%) cases were stromal invasion grade 3. Micropapillary pattern was positive in 80% of grade 3 cases. For stromal invasion grade 3 cases, the 5-year survival rate of patients with micropapillary pattern-positive carcinomas was 63%, which was significantly worse than 94% of those with micropapillary pattern-negative carcinomas (P=0.0196). The latter was very close to that for patients with stromal invasion grade 0-2 (95%). Moreover, small cluster invasion was observed at sites of stromal invasion significantly more often in micropapillary pattern-positive cases than negative cases. Thus, the stromal invasion grading system is reproducible and correlates with prognosis even in pT1 lung adenocarcinomas. Moreover, among patients with stromal invasion grade 3 carcinomas, favorable prognosis is noted in micropapillary pattern-negative cases. The micropapillary pattern subclassification provides an advantage to the stromal invasion grading system and reconfirms the importance of micropapillary pattern as a prognostic marker. Our study is the first to point to the possible association of micropapillary pattern-positive carcinomas and small cluster invasion.