Long-term Follow-up of Laparoscope-Assisted Living Donor Hepatectomy.

BACKGROUND: We have introduced and performed laparoscope-assisted surgery in living donor hepatectomy. The objective of this study was to investigate the long-term results of laparoscope-assisted living donor hepatectomy. METHODS: From 2006 to 2016, laparoscope-assisted living donor hepatectomy was performed in 11 patients (laparoscopic group), and conventional open living donor hepatectomy was performed in 40 patients (conventional group). Intraoperative and postoperative complications were evaluated according to the Clavien-Dindo classification and analyzed in the laparoscopic group for comparison with the conventional group. RESULTS: The median postoperative follow-up period was 88 months (range, 58-120 months) in the laparoscopic group. One donor in the conventional group died from a motor vehicle crash 16 months after surgery. All others were alive and returned to their preoperative activity level. Regarding intraoperative and early (≤90 days after surgery) postoperative complications, 1 patient (1/11, 9%) showed biliary fistula (Grade IIIa) in the laparoscopic group. In the conventional group, 6 patients (6/40, 15%) showed surgical complications of Grade I in 2 patients and Grade II in 4 patients. Regarding late (>90 days after surgery) postoperative complications, biliary stricture was observed in 1 patient of the laparoscopic group; this patient developed hepatolithiasis 6 years after surgery, and endoscopic lithotomy and extracorporeal shockwave lithotripsy were performed, resulting in successful treatment. Late complications were not observed in the conventional group. CONCLUSION: One donor in the laparoscopic group showed Grade IIIa late complications. The introduction of laparoscopic surgery to living donor hepatectomy should be performed carefully.

Study of Immune Tolerance Cases in Adult Living Donor Liver Transplantation.

BACKGROUND: Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS: A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS: Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipient's child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS: In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.

Successful Endoscopic Management of Acute Necrotic Pancreatitis and Walled Off Necrosis After Auxiliary Partial Orthotopic Living-Donor Liver Transplantation: A Case Report.

Endoscopic management of acute necrotic pancreatitis and walled off necrosis is less invasive than surgical treatment and has become the 1st choice for treating pancreatic necrosis and abscess. We treated a case of acute necrotic pancreatitis and walled off necrosis after auxiliary partial orthotopic living-donor liver transplantation (APOLT). A 24-year-old woman was admitted to our university hospital for removal of the internal biliary stent, which had already been placed endoscopically for the treatment of biliary stricture after APOLT. She had been treated for acute liver failure by APOLT 10 years before. After we removed the internal stent with the use of an endoscopic retrograde approach, she presented with severe abdominal pain and a high fever. Her diagnosis was severe acute pancreatitis after endoscopic retrograde cholangiography (ERC). Her symptoms worsened, and she had multiple organ failure. She was transferred to the intensive care unit (ICU). Immunosuppression was discontinued because infection treatment was necessary and the native liver had already recovered sufficiently. After she had been treated for 19 days in the ICU, she recovered from her multiple organ failure. However, abdominal computerized tomography demonstrated the formation of pancreatic walled off necrosis and an abscess on the 20th day after ERC. We performed endoscopic ultrasonography-guided abscess drainage and repeated endoscopic necrosectomy. The walled off necrosis diminished gradually in size, and the symptoms disappeared. The patient was discharged on the 87th day after ERC. This is the 1st report of a case of acute necrotic pancreatitis and walled off necrosis that was successfully treated by endoscopic management after APOLT.

Successful Re-resection for Locally Recurrent Retroperitoneal Liposarcoma at Four Years After Ex Vivo Tumor Resection and Autotransplantation of the Liver: A Case Report.

Surgical resection should be considered for isolated locally recurrent retroperitoneal liposarcomas. We experienced a case of successful re-resection for locally recurrent retroperitoneal liposarcomas 4 years after ex vivo tumor resection and autotransplantation of the liver. A 75-year-old man was admitted to our hospital. His diagnosis was local recurrence of liposarcomas. He had previously undergone ex vivo tumor resection and autologous orthotopic liver transplantation for a retroperitoneal tumor 4 years earlier. The resected tumor size was 23.5 × 15.5 × 12.5 cm. The tumor was revealed by means of histopathologic study to be a myxoid liposarcoma. Follow-up computerized tomography showed 2 recurrent tumors in the retropancreatic and para-aortic lesions. Although adhesion was severe within the operative field, we successfully performed complete en bloc re-resection of each recurrent tumor. The operative time was 250 minutes, and blood loss was 300 mL. The resected tumor sizes were 3.9 × 3.2 × 1.5 cm and 4.5 × 3.3 × 3.0 cm. The tumors were revealed by means of histopathologic study to be dedifferentiated liposarcomas. Postoperative complications included intestinal obstruction and colocutaneous fistula formation, both of which were treated surgically. The patient was discharged in an ambulatory state at 80 days after re-resection of the recurrent tumors. At the time of writing, he was alive with no evidence of recurrence, 14 months after re-resection and 62 months after primary ex vivo tumor resection. This is the first case of successful surgical re-resection for locally recurrent liposarcoma after ex vivo tumor resection and autotransplantation of the liver.

Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report.

BACKGROUND: Long-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified. METHODS: We have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function. RESULTS: The patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 µg/d. CONCLUSIONS: Our patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.

The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer.

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. High-fat diet (HFD) and obesity, which is now endemic, increase breast cancer risk and have been associated with worse prognosis. HFD accelerated the onset of tumors with more advanced lesions and increased triple-negative spontaneous breast tumors and HDAC activity in MMTV-PyMT transgenic mice. Oral administration of clinically relevant doses of FTY720 suppressed development, progression and aggressiveness of spontaneous breast tumors in these mice, reduced HDAC activity and strikingly reversed HFD-induced loss of estrogen and progesterone receptors in advanced carcinoma. In ERα-negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, treatment with FTY720 also re-expressed ERα and increased therapeutic sensitivity of ERα-negative syngeneic breast tumors to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that a multipronged attack with FTY720 is a novel combination approach for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.

Preoperative predictors of vascular invasion in hepatocellular carcinoma.

AIMS: Vascular invasion is an established adverse prognostic factor in hepatocellular carcinoma (HCC). The aim of the current study was to identify the preoperative predictors of vascular invasion in patients undergoing partial hepatectomy for HCC. METHODS: A retrospective analysis of 227 consecutive patients who underwent partial hepatectomy for HCC was conducted. Vascular invasion was defined as gross or microscopic involvement of the vessels (portal vein or hepatic vein) within the peritumoral liver tissue. RESULTS: Seventy-six (33%) patients had vascular invasion. Among the preoperative factors, only the tumour size (relative risk, 16.78; p<0.01) and the serum alpha-fetoprotein (AFP) level (relative risk, 3.57; p<0.01) independently predicted vascular invasion. As the tumour size increased, the incidence of vascular invasion increased: < or =2 cm, 3%; 2.1-3 cm, 20%; 3.1-5 cm, 38%; and > 5 cm, 65%. The incidence of vascular invasion was 32% in patients with serum AFP levels < or =1000 ng/mL, compared to 61% in patients with higher serum AFP levels (p<0.01). Patients with both tumours >5 cm and serum AFP levels >1000 ng/mL had an 82% incidence of vascular invasion. CONCLUSIONS: The tumour size and serum AFP level, alone or in combination, are useful in predicting the presence or absence of vascular invasion before hepatectomy for HCC.

Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats.

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.

Dietary docosahexaenoic acid can alter the surface expression of CD4 and CD8 on T cells in peripheral blood.

The effect of dietary docosahexaenoic acid (DHA) on T cell states in peripheral blood was investigated. Weanling male C57Bl/6N mice were kept on one of three 10% fat diets containing various amounts of DHA and linoleic acid for 4 weeks. Changing the concentration of dietary DHA did not alter the proportion of T cells expressing CD4 or CD8. However, increasing the concentration of dietary DHA lowered the expression of CD4 and CD8 on the cell surface. The decreased expression of these surface molecules involved in T cell proliferation has serious implications in the role of DHA as an immunosuppressant.

Effects of dioxins on human health: a review.

The toxicity of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) has been known since 1950s. TCDD is a by-product of herbicide 2,4-dichloroacetophenol (2,4-D) and 2,4,5-trichloroacetophenol (2,4,5-T), but it was first found in fryash of municipal incinerator in 1979 in Japan. In 1998, the survey of municipal incinerators revealed that 105 out of 1,641 produced above the allowed emission level of 80 ng TEQ/m3. Total annual release of dioxins is estimated to be about 5,000 g TEQ in 1997 in Japan. Japanese government started a comprehensive survey for dioxin levels in milk and blood of residents around incinerators, and their health effects. Human effects by dioxin exposures in Western countries were mostly acute and at high level in accidentally and/or occupationally. Health effects of low-dose and long lasting exposure has not been well understood. Certain amount of polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) is accumulated in our body. Mother's milk is also contaminated by PCDD/PCDF. Health effects of the polychlorinated chemicals are summarized, and the necessity of regulations and recommendations for making a guideline is discussed in this review.

Changes in dietary fiber intake among Japanese in the 20th century: a relationship to the prevalence of diverticular disease.

In view of the fact that Japanese dietary patterns have been undergoing rapid "Westernization," in part characterized by decrease in fiber, we assessed dietary and crude fiber content in the Japanese diet using food consumption tables for the period from 1911 to 1980, and studied the trend in the reported prevalence of diverticular disease of the colon. Fiber content declined in diphasic pattern: the first decline, which probably had started in the late 19th century, progressed until the Second World War. Although records during the war period were unavailable, the high fiber content of the Japanese diet in the period immediately after the war reflects the tendency to supplement rice with more fiber-rich cereals, and to increase the amount of rice through reduced polishing during the war time. The second decline in fiber content in the Japanese diet, which started in the 1950s and progressed throughout the period of "high economic growth," was mainly due to the decrease in cereal consumption. The changes in crude fiber content in the Japanese diet after the Second World War resemble the pattern of rapid decline noted in the United States during the 1930s to the 1950s. The prevalence of diverticular disease in both countries also shows sudden steep upward turns during the period between 1930 and 1950 in the United States and the late 1970s in Japan, suggesting the presence of threshold level(s) of fiber intake for the effective prevention of diverticular disease. The prevalence of diverticular disease is still relatively low in Japan. However, if the current dietary trend continues, it may rise to a level currently found in the "Western" countries in the coming few decades.

[Scanning electron microscopic observations of calcium pyrophosphate crystals of joint tissues and synovial fluid (author's transl)].

The deposition and ultrastructure of calcium pyrophosphate (CPPD) crystals in joint tissues of pseudogout patients and cadavers were studied. Nine calcified menisci, 2 articular cartilages and 6 samples of synovial fluid were examined by scanning electron microscopy (SEM). Some of them were examined by analytical electron microscopy (EMMA). In the samples of menisci and cartilages, the findings were compared with those in the soft X-ray examinations and polarized light microscopy. The results are summarized as follows: 1) SEM observation of the cut surfaces of calcified menisci and cartilages showed a three-dimensional ultrastructure for the CPPD crystals. The crystals in the synovial fluid taken from pseudogout knees were also clearly demonstrated by this method. The EMMA analysis provided the possibility to examine the structure and content of the crystals simultaneously. 2) Crystal deposition in the meniscus varied with the depth of the tissues; it was diffuse in the collagen framework of the superficial layer, but showed accumulation in the deep layer where a clear line of demarcation between the collagen framework and crystals was seen. 3) The crystals in the meniscus were rod, granular or rectangular in shape, and 0.2-6.5 micro by 0.2-3.5 micro in size. Crystals from the articular cartilage were granular or rod-like in shape, and 0.2-3.5 micro by 0.2-1.0 micro in size. Most of the crystals found in the synovial fluid were rod-shaped. 4) X-ray microanalysis of the meniscus crystals by EMMA showed the same pattern of PK alpha, CaK alpha, and CaK beta content as that of CPPD crystals commercially available. The P/Ca ratio was about 0.7. 5) SEM and EMMA examination can be very useful for accurate identification of the form and content of the tiny crystals in joint tissues and synovial fluid. This can also be useful in proving a diagnosis of crystal-induced synovitis.

delta-aminolevulinic acid dehydratase in low level lead exposure.

No statistically significant correlation was observed between log delta-aminolevulinic acid dehydratase (ALAD) activity and blood lead levels (Pb-B) in rural or urban habitants (p greater than .5 and P greater than .1, respectively) in whom no occupational source of lead was known. However, when the values the the two groups were pooled, there was a fairly good negative correlation (r = 0.509, P less than .01). Stepwise correlation coefficient analysis indicated the existance of a threshold value of Pb-B (around 15 mug/100 ml) below which ALAD activity had nor orderly relationship with the Pb-B. In contrast with married couples, parents and their children showed a remarkably high interrelationship in values of ALAD. It is concluded that in low level lead exposure primarily genetic factors influence the activity of ALAD and, thus ALAD is useful for the evaluation of lead exposure only when the lead level is higher than the threshold.