Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT

Journal of Gastroenterology - REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma...     

Transient liver injury caused by gefitinib]

Gefitinib blocks epidermal growth factor receptor autophosphorylation and subsequently the signal transduction pathways implicated in proliferation, metastasis, invasion, and angiogenesis. Reported adverse reactions to gefitinib include liver injury that is not fully understood. Liver injury was observed in 5 (12.2%) of 41 patients with non-small cell lung cancer who received gefinitib monotherapy. Onset of liver injury was seen between 28 and 56 days after initiation of administration. Two patients had Grade 2 liver injury and 3 patients, Grade 3. In 4 patients, liver injury was temporary, lasting during a period of continuous gefitinib administration. In another patient, gefitinib was discontinued because of the onset of liver injury, which improved when gefitinib administration was restarted. Gefitinib is necessary in most patients whose lung cancer is refractory to cytotoxic chemotherapy, because no other treatment regimens are available at present. The rate of liver injury in cases treated with gefitinib is high, and so it is necessary to observe liver function carefully, but the liver injury due to this drug is often transient. However, the use of gefitinib in many cases appears to be a necessity.     

Experience with 1904 laparoscopic cholecystectomies at a private hospital

The purpose of this paper is to describe our recent experience in performing laparoscopic cholecystectomies of which we performed 1904, from January 1991 to May 1997, at our private hospital, mainly to treat cholecystolithiasis. The patients included 1563 with gallbladder stones (82.0%), 82 with cholecystocholedocholithiasis (4.3%), 104 with adenomyomatosis (5.5%), 132 with polyps (6.9%), and 23 with gallbladder cancer (1.3%). A difficult pericholecystic dissection led to conversion to open surgery in 61 patients. The average operation time was 63 min. Bile duct injury or cystic artery bleeding occurred in 3 patients with acute cholecystitis, and small intestine injury occurred in 1 patient, while bile leakage or a right subphrenic abscess occurred in 6 patients postoperatively. Although this series included 69 patients with previous upper abdominal surgery, 14 with liver cirrhosis, 267 with a nonvisualized gallbladder, and 148 with acute cholecystitis, the overall conversion rate was only 3.2% and morbidity only 0.5%. Although almost all patients with cholelithiasis are now considered potential candidates for a laparoscopic cholecystectomy, difficulties during cholecystectomy have been encountered in patients with acute cholecystitis. Surgeons should thus be fully prepared to convert to open surgery whenever difficulties are encountered, in order to avoid complication.     

Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome

Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.     

Promotion of Transplanted Bone Marrow-derived Cell Migration into the Periodontal Tissues due to Orthodontic Mechanical Stress

Background: Bone marrow-derived cells (BMCs) have abilities of cell migration and differentiation into tissues/organs in the body and related with the differentiation of teeth or periodontal tissue including fibroblasts. Then, we examined the effect of orthodontic mechanical stress to the transplanted BMC migration into periodontal tissues using BMC transplantation model.Material and Method: BMC from green fluorescence protein (GFP) transgenic mice were transplanted into 8-week-old female C57BL/6 immunocompromised recipient mice, which had undergone 10 Gy of lethal whole-body-irradiation. Five mice as experimental group were received orthodontic mechanical stress using separator between first molar (M1) and second molar (M2) 1 time per week for 5 weeks and 5 mice as control group were not received mechanical stress. The maxilla with M1 and M2 was removed and was immunohistochemically analyzed using a Dako Envision + Kit-K4006 and a primary anti-GFP-polyclonal rabbit antibody. Immunohistochemically stained was defined as positive area and the pixel number of positive area in the periodontal tissue was compared with the previously calculated total pixel number of the periodontal tissue.Results: The immunohistochemistry revealed that GFP positive cells were detected in the periodontal tissues, both in the experimental and control specimens. The ratio of pixel number in the examination group showed 5.77 ± 3.24 % (mean ± SD); and that in the control group, 0.71±0.45 % (mean ± SD). The examination group was significantly greater than that of control group (Mann-Whitney U test: p<0.001).Conclusion: These results suggest that orthodontic mechanical stress accelerates transplanted BMC migration into periodontal tissues.     

A Single Case of Single-Port Access Laparoscopic Appendectomy During the Puerperium

Laparoscopic appendectomy is now widely practiced for the treatment of acute appendicitis. As result of increased demand for minimally invasive surgery, single-incision access was introduced and is being performed in various abdominal surgeries. Conventional laparoscopic appendectomy (LA) is gradually being performed in pregnant women. A 33-year-old woman was referred to our department at 39 weeks and 1 day of gestation due to abdominal pain. She was aware of her gastroepiploic pain even after the delivery. Though it was past 2 days, she was not recovering from right lower abdominal pain, so she was transferred to the Department of Gynecology at our hospital on the same day. Although an antibiotic was administered, the right abdominal pain did not improve, and she was referred to our department from the Department of Gynecology. We performed single-port LA (SP-LA). The total operation time was 63 minutes, and the estimated blood loss was 0 mL. She was discharged with no complications on postoperative day 7. We report our initial experience with single-port LA (SP-LA) using the glove technique for treatment of acute appendicitis in a postpartum woman. SP-LA using the glove technique was performed successfully during the puerperium without prolongation of operation time. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.Key words: PLA (single-port laparoscopic appendectomy), PuerperiumThe advantages of laparoscopic appendectomy (LA) over open appendectomy (OA) are widely known and include decreased pain, shorter convalescence, and earlier return to work. Especially, LA is advantageous for treating acute appendicitis in pregnant women. Because the appendix of a pregnant woman is shifted from its normal position, OA may leave a larger operative scar than normal. In recent years, efforts of laparoscopic surgeons have resulted in a reduction in both the diameter of the access ports and the number of ports needed.¹ In addition, natural orifice transluminal endoscopic surgery (NOTES) is being developed as another form of minimally invasive surgery.² As a part of this process, the single-incision laparoscopic surgery (SILS) technique is presently being developed for various laparoscopic surgeries.³ SILS is a virtually scarless technique in which the single-port access site is hidden in the umbilicus. We think that the primary advantage of single-port laparoscopic appendectomy (SP-LA) is the superior cosmetic result compared with multi-port access LA. We report a very rare case in which SP-LA was performed to treat acute appendicitis during the puerperium. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.     

Mortality risk attributable to atrial fibrillation in middle-aged and elderly people in the Japanese general population: nineteen-year follow-up in NIPPON DATA80.

BACKGROUND: The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. METHODS AND RESULTS: A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age > or =30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). CONCLUSION: AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events.     

A father and son with Turcot's syndrome: Evidence for autosomal dominant inheritance

Typical Turcot's syndrome is characterized by the association of a brain glioma together with multiple colonic polyposis, in which the number of polypoid lesions is small and the association of colonic cancer occurs at a younger age than in familial adenomatous polyposis. We describe a family in which both the father and his son presented with typical Turcot's syndrome without parental consanguinity. This is the first report of a family that is considered to follow an autosomal dominant inheritance. After reviewing 25 documented cases in which the average age of death was 20.3 years old, it was learned that the major cause of death was brain tumor (76 percent) and the minor cause was colon cancer (16 percent). Patients were very young and, therefore, unlikely to have produced a child before their death. These facts seem to support the theory that Turcot's syndrome is an autosomal dominant disorder.