Intractable Biliary Strictures After Living Donor Liver Transplantation: A Case Series.

BACKGROUND: Biliary stricture (BS) is a severe complication after liver transplantation. It is difficult to treat, especially after living donor liver transplantation (LDLT). We successfully treated 4 patients for intractable BS after LDLT. All patients had developed cholangitis with stenosis of bile ducts anastomosis. CASE 1: . A 65-year-old woman underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Internal plastic stents inserted by endoscopic retrograde cholangiography (ERC) were changed quarterly for the next 2 years. CASE 2: A 55-year-old man underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Insertion of internal plastic stents by ERC was attempted; however, the posterior bile duct branch showed complete obstruction. After percutaneous transhepatic biliary drainage (PTCD), the stents were inserted using the rendezvous technique of ERC and were changed by ERC quarterly for the next 3 years. CASE 3: A 22-year-old man underwent LDLT with left lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and stents were changed quarterly for the next 2 years. CASE 4: A 60-year-old man underwent LDLT with right lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and changed to a metallic stent after 1 year. Three months later the stent was extracted using the rendezvous technique of double balloon enteroscopy. CONCLUSION: BS of complete obstruction type after LDLT is difficult to treat. Appropriate procedures should be chosen based on the types of strictures and biliary reconstruction methods.

Histomorphological investigation of intrahepatic connective tissue for surgical anatomy based on modern computer imaging analysis.

BACKGROUND/PURPOSE: Computer-assisted tissue imaging and analytical techniques were used to clarify the histomorphological structure of hepatic connective tissue as a practical guide for surgeons. METHODS: Approximately 5000 histological slides were prepared from liver specimens of five autopsied patients. Three-dimensional (3D) reconstruction was performed and subjected to computer imaging analysis. Scanning electron microscopy was also performed on the liver specimens. RESULTS: The 3D reconstructed images revealed the running form of the vasculature and the relationship between the hepatic lobule and connective tissue. The hepatic capsule or portal pedicle was consistently located at the periphery of the hepatic lobules. An artificial intelligence random forest approach clearly segmented hepatic cells, type I collagen (CF), type III collagen (RF), and other cells. The hepatic lobule, portal region, and hepatic capsule were significantly distinguished based on CF and RF occupancy. The capsule directly covering the liver lobule with an RF concentration up to 87% was provisionally named the proper hepatic capsule. The existence of a proper hepatic ligament with distinct occupation rates of CF and RF was also suggested. CONCLUSIONS: The identified proper hepatic capsule and ligament can be important markers for demarcating the dissecting layer during surgical procedures.

Electrohydraulic lithotripsy and rendezvous nasal endoscopic cholangiography for common bile duct stone: A case report.

BACKGROUND: In patients with large stones in the common bile duct (CBD), advanced treatment modalities are generally needed. Here, we present an interesting case of a huge CBD stone treated with electrohydraulic lithotripsy (EHL) by the percutaneous approach and rendezvous endoscopic retrograde cholangiography (ERC) using a nasal endoscope. CASE SUMMARY: A 91-year-old woman underwent ERC for a symptomatic large CBD stone with a diameter of 50 mm. She was referred to our institution after the failure of lithotomy by ERC, and after undergoing percutaneous transhepatic biliary drainage. We attempted to fragment the stone by transhepatic cholangioscopy using EHL. However, the stones were too large and partly soft clay-like for lithotripsy. Next, we attempted lithotomy with ERC and cholangioscopy by the rendezvous technique using a nasal endoscope and achieved complete lithotomy. No complication was observed at the end of this procedure. CONCLUSION: Cholangioscopy by rendezvous technique using a nasal endoscope is a feasible and safe endoscopic method for removing huge CBD stones.

Skeletal muscle loss during systemic chemotherapy for colorectal cancer indicates treatment response: a pooled analysis of a multicenter clinical trial (KSCC 1605-A).

BACKGROUND: Sarcopenia or degenerative loss of skeletal muscle mass is related to poor prognosis in patients with cancer. This study aimed to clarify the clinical significance of skeletal muscle loss (SML) during chemotherapy for metastatic colorectal cancer (mCRC). METHODS: A total of 249 patients who were secondarily registered in a pooled database of mCRC patients with the first-line systemic chemotherapy and prospectively enrolled in six clinical trials of Kyushu Study Group of Clinical Cancer were included in this study. Skeletal muscle area was calculated from computed tomography images before and 3 and 6 months after treatment. Baseline sarcopenia and SML (cut-off value = 9%) were evaluated. RESULTS: Baseline sarcopenia was observed in 135 of 219 patients who were evaluated before treatment. They tended to be male; older; and have lower body mass index, lower visceral and subcutaneous fat contents, and a lower waist circumference (P < 0.01); however, baseline sarcopenia was not associated with prognosis. SML at 3 months was associated with an incidence of adverse events (P = 0.01), poor objective response rate (ORR) (P < 0.01), and poor progression-free survival (PFS) (P = 0.03), and it was an independent predictive factor for poor ORR (P < 0.01) and PFS (P = 0.04). CONCLUSION: SML at 3 months after systemic chemotherapy for mCRC was associated with poor treatment response. Thus, clarifying the importance of SML prevention guarantees a more effective chemotherapy.

Sarcopenia is an independent predictor of complications after colorectal cancer surgery.

PURPOSE: The significance of sarcopenia after colorectal cancer (CRC) resection has only been discussed with relatively small samples or short follow-up periods. This study aimed to clarify the clinical significance of sarcopenia in a large-sample study. METHODS: We retrospectively analyzed the relationship between sarcopenia and clinical factors, surgical outcomes, and the survival in 494 patients who underwent CRC surgery between 2004 and 2013. Sarcopenia was defined based on the sex-specific skeletal muscle mass index measured by preoperative computed tomography. RESULTS: Sarcopenia was associated with sex (higher rate of male, P < 0.0001), and low body mass index (P < 0.0001), but not age or tumor stage. Sarcopenia was associated with higher incidence of all postoperative complications (P = 0.02), especially for patients with Clavien-Dindo classification grade ≥2 (CDC; P = 0.0007). Postoperative hospital stays were significantly longer for sarcopenic patients than for non-sarcopenic patients (P = 0.02). In a multivariate analysis, sarcopenia was an independent predictor for postoperative complications (P = 0.01, odds ratio 1.82, 95% confidence interval 1.13-3.00). Among postoperative complications (CDC grade ≥2), sarcopenia was correlated with non-surgical-site infections (P = 0.03). Sarcopenia was not correlated with the overall or recurrence-free survival. CONCLUSIONS: Sarcopenia was an independent predictive factor for postoperative complications after CRC surgery.

Chd5 Regulates MuERV-L/MERVL Expression in Mouse Embryonic Stem Cells Via H3K27me3 Modification and Histone H3.1/H3.2.

Chd5 is an essential factor for neuronal differentiation and spermatogenesis and is a known tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3.1/H3.2 function.

New evidence of the reproductive organs of Glossopteris based on permineralized fossils from Queensland, Australia. II: pollen-bearing organ Ediea gen. nov.

Ediea homevalensis H. Nishida, Kudo, Pigg & Rigby gen. et sp. nov. is proposed for permineralized pollen-bearing structures from the Late Permian Homevale Station locality of the Bowen Basin, Queensland, Australia. The taxon represents unisexual fertile shoots bearing helically arranged leaves on a central axis. The more apical leaves are fertile microsporophylls bearing a pair of multi-branched stalks on their adaxial surfaces that each supports a cluster of terminally borne pollen sacs. Proximal to the fertile leaves there are several rows of sterile scale-like leaves. The pollen sacs (microsporangia) have thickened and dark, striate walls that are typical of the Arberiella type found in most pollen organs presumed to be of glossopterid affinity. An examination of pollen organs at several developmental stages, including those containing in situ pollen of the Protohaploxypinus type, provides the basis for a detailed analysis of these types of structures, which bear similarities to both compression/impression Eretmonia-type glossopterid microsporangiate organs and permineralized Eretmonia macloughlinii from Antarctica. These fossils demonstrate that at least some Late Permian pollen organs were simple microsporophyll-bearing shoot systems and not borne directly on Glossopteris leaves.

[Multi-modarity treatment for colon liver metastases using biliary stent-report of a case].

We report the case of a 69-year-old male patient with diagnoses of sigmoid colon cancer, ascending colon cancer, and metastatic liver cancer. We performed sigmoidectomy, right hemicolectomy, and central venous port placement. Because the liver metastasis was multifocal, chemotherapy was first initiated and then hepatic resection was performed. However, during chemotherapy, ileus, with a peritoneal dissemination to the small intestine, developed. Small intestine resection and radiation therapy to the pelvic region of the transition were further performed. Thereafter, obstructive jaundice due to obstruction of the bile duct in the hilar area developed, and therefore, we inserted a biliary stent. However, 2 years 9 months after the first medical examination, this patient died of colon cancer. The guidelines above, still chemotherapy developed, treatment policy of recurrent colorectal cancer, have recommended surgical resection with respect to what resectable as local therapy. This case shows that combination therapy with chemotherapy, surgical therapy, radiation therapy, and local therapy such as biliary stenting, is useful.

[A case of long-term survival following combined modality therapy for peritoneal disseminated recurrence of duodenal cancer].

A 65-year-old man was diagnosed with primary duodenal cancer and he underwent pancreaticoduodenectomy in June 2006. S-1 was administered as the postoperative adjuvant chemotherapy. A peritoneal disseminated recurrence was diagnosed together with a right reniportal node and right hydronephrosis in February 2007. A ureteral stent was inserted. DOC +S-1 combination therapy was administered from March 2007. Following progression of the recurrence, CDDP+S-1 combination therapy was administered from August 2007. Temporal diminution of the recurrence was achieved with radiotherapy from May to June 2009. Following re-progression of the recurrence, biweekly CPT-11 therapy was administered from February 2010. Weekly PTX therapy was administered from January 2011. The patient died due to progression of the recurrence in June 2011, 5 years after the operation. Our patient maintained a good quality of life and achieved long-term survival by combined modality therapy for peritoneal disseminated recurrence of duodenal cancer.

[A case of long-term survival due to combined modality therapy for liver metastasis of colon cancer].

The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local therapy.

[A case successfully treated with abdominoperineal resection after preoperative chemoradiation therapy for anal cancer].

A 46-year-old female was diagnosed with anal squamous cell carcinoma. Chemoradiation therapy was administered for a first-line therapy. Two courses of enforced 5-FU/MMC combination therapy were administered along with radiotherapy (60 Gy). This chemoradiation therapy had complete response. However, three months after, anal cancer had a local recurrence. Since there was no distant metastasis, abdoninoperineal resection was performed. No complications were observed after the operation. We conclude that abdominoperineal resection may be effective in the treatment of anal cancer in cases which the local recurrence was observed after chemoradiation therapy.

[A case of long-term survival by combined modality therapy for liver and pulmonary metastasis of rectal cancer].

We report a case of rectal cancer diagnosed in 2001, which enforced a rectal low anterior resection. Then, metastatic liver cancer and metastatic lung cancer recurred and we enforced an operation for both. Furthermore, metastatic lung cancer recurred again and enforced chemotherapy with radiation and systemic chemotherapy for approximately seven years. The metastatic lung cancer was reduced now in 2011, so that the chemotherapy has not been used since then. In our case, we mainly performed a surgical and radiation therapy for a local recurrent site therapy in the first half because we did not have much choice for a systemic chemotherapy like we have now. In the later half, we mainly performed a systemic chemotherapy to control the local recurrent site. A treatment policy for colon cancer recommends a surgical treatment by the guidelines, or even though chemotherapy has been developed at present, if a local therapy is practical. There were many cases where metastases had occurred right after surgery so a local site therapy by excision was good at all unconditionally. However, as a result of our case in a local site therapy combined with whole body chemotherapy, we report here that a long- term survival was obtainable. We also include a brief literature review.

[A case successfully treated with subtotal esophagectomy after preoperative second-line chemotherapy for cT4 esophageal cancer].

A 69-year-old male was diagnosed with type 2 advanced esophageal cancer in the upper and middle thoracic esophagus which invaded the left main bronchus and the aorta. Radio-chemotherapy was administered since a radical resection could not be performed due to the invasion. Two courses of enforced FP combination therapy (5-FU and CDDP) were administered along with radiotherapy. Although this radio-chemotherapy was effective to some degree in tumor reduction, a radical resection still could not be performed due to the invasion of the left main bronchus and the aorta. Thus, we administered four more courses of DCF combination therapy (docetaxel, CDDP and 5-FU). This chemotherapy reduced the esophageal cancer mass significantly, and subtotal esophagectomy was performed. No complications were observed after the operation. We conclude that DCF combination therapy may be effective in the treatment of esophageal cancer in cases which the desired effect cannot be achieved by FP combination therapy alone.

New evidence of reproductive organs of Glossopteris based on permineralized fossils from Queensland, Australia. I. Ovulate organ Homevaleia gen. nov.

This study describes Homevaleia gouldii H. Nishida, Pigg, Kudo et Rigby gen. et sp. nov., an ovule-bearing glossopterid organ, based on a combination of recently collected permineralized specimens from the Late Permian Homevale Station locality in the Bowen Basin of Queensland, Australia, and on previously studied material from the 1977 Gould and Delevoryas study. Homevaleia, which resembles the compression-impression genus Dictyopteridium, is an inrolled megasporophyll with a distinct keel that bears numerous (over 70) stalked ovules on its adaxial surface. Ovules are small, oval, with an elaborate mesh-like structure that is developed from the outermost integumentary layers. Specimens interpreted as representing different developmental stages show there is an apparent interrelationship between megagametophyte development and the opening of the surrounding fertile structure for pollination. Together, new information provided by this material enables better understanding of glossopterid reproductive structure and its function in one distinctive form.

Zooidogamy in the Late Permian genus Glossopteris.

We describe details of anatomically preserved fossil glossopterid ovules from the Late Permian of Queensland, Australia, that contain several pollen tubes at various stages of releasing flagellated sperm. Each sperm is approximately 12.7 microm long and 13.9 microm wide, with a conspicuous spiral structure comprised of a series of dots that resemble the position of basal bodies of flagella aligned along the multilayered structure (MLS). This configuration is similar to the helically arranged flagella in the sperm of cycads, Ginkgo, and many pteridophytes. However, the motile gametes of Glossopteris are considerably smaller than those of Ginkgo and cycads, and more similar in size, number of basal bodies, and number of gyres in their helix to pteridophyte forms. Glossopteris thus shares the intermediate stage of motile male gamete formation and apparently that of haustorial pollen tubes with cycads and Ginkgo.