Reappraisal of tacrolimus levels after liver transplant for HCC: A multicenter study toward personalized immunosuppression regimen.

Post-liver transplant (LT) immunosuppression is necessary to prevent rejection; however, a major consequence of this is tumor recurrence. Although recurrence is a concern after LT for patients with HCC, the oncologically optimal tacrolimus (FK) regimen is still unknown. This retrospective study included 1406 patients with HCC who underwent LT (2002-2019) at 4 US institutions using variable post-LT immunosuppression regimens. Receiver operating characteristic analyses were performed to investigate the influences of post-LT time-weighted average FK (TWA-FK) level on HCC recurrence. A competing risk analysis was employed to evaluate the prognostic influence of TWA-FK while adjusting for patient and tumor characteristics. The AUC for TWA-FK was greatest at 2 weeks (0.68), followed by 1 week (0.64) after LT. Importantly, this was consistently observed across the institutions despite immunosuppression regimen variability. In addition, the TWA-FK at 2 weeks was not associated with rejection within 6 months of LT. A competing risk regression analysis showed that TWA-FK at 2 weeks after LT is significantly associated with recurrence (HR: 1.31, 95% CI: 1.21-1.41, p < 0.001). The TWA-FK effect on recurrence varied depending on the exposure level and the individual's risk of recurrence, including vascular invasion and tumor morphology. Although previous studies have explored the influence of FK levels at 1-3 months after LT on HCC recurrence, this current study suggests that earlier time points and exposure levels must be evaluated. Each patient's oncological risk must also be considered in developing an individualized immunosuppression regimen.

Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines.

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and is associated with late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.

Trans-Pacific class transmission over a standard cladding ultralow-loss 4-core fiber.

The total capacity of optical submarine cable systems as a global communication infrastructure must be continuously enlarged. Multi-core fibers (MCFs) have been studied as methods to maximize the total cable capacity under electrical power and cable space limitations. In particular, standard cladding MCFs, which are expected to have high productivity and mechanical reliability, are attractive for early deployment in submarine cable systems. In this paper, we demonstrate high-capacity trans-Pacific class transmission using standard cladding uncoupled 4-core fibers, achieving a transmission capacity of 55.94 Tbit/s over 12,040 km. In addition, based on the results of this and our previous coupled MCF transmission experiments, we summarize the characteristics of coupled and uncoupled MCFs applied to optical submarine cable systems.

Spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers.

To realize simplified cost-efficient optical networks with routing flexibility and scaling potential, a spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers is proposed herein, which can route all spatial channels together as a unit. Numerical simulations and experiments were performed, and the results show that the signal paths for a 6-mode 19-core fiber can be simultaneously switched to the target output ports using the proposed method, and the mode-field patterns of the diffracted light can be maintained after joint switching. Further, the maximum port crosstalk can be reduced considerably from -11.6 to -25.1 dB by changing the position of the output port in the proposed method.

Distal allograft pancreatectomy for graft salvage after pancreas transplantation.

Early pancreas allograft failure most commonly results from vascular thrombosis. Immediate surgical intervention may permit pancreas allograft salvage, typically requiring thrombectomy. In cases of partial allograft necrosis secondary to splenic arterial thrombosis, distal allograft pancreatectomy may allow salvage of at least half of the pancreas allograft with retention of function. We retrospectively reviewed four cases of simultaneous pancreas and kidney recipients who required distal allograft pancreatectomy for splenic artery thrombosis with necrosis of the distal pancreas. Three of the four maintained long-term allograft function with euglycemia independent of insulin at six months to six years of follow-up, and all patients continue to maintain normal renal allograft function. Early diagnosis and early intervention are essential in order to salvage the pancreas allograft in the case of thrombosis. Distal allograft pancreatectomy can be performed safely and result in excellent long-term outcomes in select patients.

Donor-recipient body size mismatch has no impact on outcomes after deceased donor whole liver transplantation: Role of donor liver size measurement.

The role of donor-recipient body size mismatch (DRSM) on outcomes after whole liver transplantation (LT) is not clearly defined. At our center, in presence of considerable DRSM, objective assessment of the donor liver by a radiology or intraoperative evaluation by procuring surgeon was incorporated. To evaluate the impact of DRSM on graft outcomes with this approach, adult deceased donor whole liver transplants between July 2001 and December 2017 at our center were studied. DRSM was considered when the donor-recipient body surface area (BSA) ratio (DR-BSAr) was either <0.69 or >1.25. There were 54 (3.2%) transplants with DR-BSAr <0.69 and 61 (3.6%) with DR-BSAr >1.25. One-year graft survival was 85% vs. 89% vs. 89%; (p = .64) for transplants with DR-BSArs of <0.69, 0.69-1.25, and >1.25, respectively. Early allograft dysfunction (EAD) (28% vs. 27% vs. 37%; p = .07), post-transplant coagulopathy, bilirubinemia, and renal function were also comparable. In conclusion, with the actual measurement of the donor liver and recipient abdominal cavity, significant DRSM did not have a negative impact on early and long-term outcomes. Routine measurement of donor liver size by radiology may be incorporated in liver allocation to improve utilization.

Weakly coupled 10-mode-division multiplexed transmission over 48-km few-mode fibers with real-time coherent MIMO receivers.

For weakly coupled mode-division multiplexed (MDM) transmission systems, we design and implement optical coherent receiver prototypes with real-time multiple-input multiple-output (MIMO) digital signal processing to equalize two degenerate linearly polarized modes with dual polarization. Using field programmable gate array circuits, we implement real-value 8 × 2 MIMO adaptive equalization with externally separated phase compensators based on the least mean square algorithm, which enables not only training equalization but also fast carrier-phase tracking. With the optical coherent MIMO receiver prototype, we demonstrate real-time weakly coupled 10 × MDM wavelength-division multiplexed dual-polarization quadrature phase shift keying transmission over 48-km few-mode fibers. This report shows a record number of multiplexed spatial modes, namely, 10 modes with dual polarization, in real-time MDM transmission experiments.

[Surgical Resection after Transarterial Chemoembolization for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus-Report of a Long-Term Survivor].

A 78-year-old woman with jaundice was referred to our hospital. On admission, serological testing for viral hepatitis was negative and serum levels of AFP and PIVKA-Ⅱ were elevated(925 ng/mL and 6,820 mAU/mL, respectively). Computed tomography revealed a main tumor measuring 3 cm in size at segment 1 of the liver and bile duct tumor thrombus extending to the right hepatic duct. A diagnosis of hepatocellular carcinoma with a bile duct tumor thrombus was made. After endoscopic biliary drainage for obstructive jaundice and transarterial chemoembolization for the lesions, she underwent left hepatectomy, resection of the caudate lobe, extrahepatic bile duct resection, and cholecystectomy. The hepatic side of the extrahepatic bile duct was transected at the confluence of the right anterior and posterior ducts because invasion of the tumor thrombus to the right hepatic duct was suspected on cholangioscopy. Histological examination revealed the tumor to be a moderately differentiated hepatocellular carcinoma with bile duct tumor thrombus. Surgical margins were negative, and vascular invasion was not found. She remains alive and well with no evidence of disease 64 months after hepatectomy.

Effective area measurement of few-mode fiber using far field scan technique with Hankel transform generalized for circularly-asymmetric mode.

We report on a measurement method for the effective area of the few-mode fiber. We derived a transform equation between a near-field pattern and a far-field pattern generalized for circularly-asymmetric higher-order modes of a cylindrical core, and enabled effective area measurement of the higher-order modes using high-dynamic-range far-field scan technique and low-crosstalk mode multiplexer. The measured effective area values agreed well with the values that were numerically predicted using a finite-element method from the refractive index profile, when the modal crosstalk was suppressed.

[Pancreaticoduodenectomy for Recurrent Retroperitoneal Liposarcoma].

A 56-year-old woman was referred to our hospital with complaints of appetite loss and abdominal distension. Enhanced abdominal computed tomography revealed a giant retroperitoneal tumor. We performed en bloc tumor resection. The histological diagnosis was of a dedifferentiated liposarcoma. One year after the initial surgery, 2 tumors were detected around the pancreas using computed tomography. We made a diagnosis of recurrent retroperitoneal liposarcoma and attempted surgical removal of the tumors. However, 1 of the tumors firmly adhered to the pancreas and duodenum; thus, we performed subtotal stomach-preserving pancreaticoduodenectomy to remove the tumors. The histological diagnosis was the same as that obtained during the initial surgery: a dedifferentiated liposarcoma. The patient remains alive and well with no evidence of disease 2 years after the initial surgery.

[Surgical Resection for Peritoneal Metastasis in Hepatocellular Carcinoma-A Report of Three Cases].

Peritoneal metastasis is relatively rare in patients with hepatocellular carcinoma(HCC). No consensus has been reached regarding the treatment of this type of metastasis. Herein, we report 3 patients who underwent resection of peritoneal metastasis due to HCC. Case 1: A 48-year-old man underwent hepatectomy twice and radiofrequency ablation(RFA)once for HCC. Eight years after the initial resection, he underwent resection of peritoneal metastasis in the pelvic floor. He is alive with disease 17 months after the last operation. Case 2: A 71-year-old man with a history of percutaneous ablation therapy for HCC 3 times underwent hepatectomy for recurrent HCC. During the laparotomy, a peritoneal metastatic tumor was found near the live tumor, and simultaneous resection of both the tumors was performed. The patient died of recurrent disease 20 months after the last resection. Case 3: A 58-year-old man underwent hepatectomy for HCC and RFA for its recurrence. Peritoneal metastasis that invaded the duodenum was detected 8 years after the hepatectomy. Although the metastatic tumor was resected, he died of the carcinoma 2 months after the resection. We concluded that resection of peritoneal metastasis provides a survival benefit for selected patients with HCC.

[A Case of Long-Term Survival after Reoperation for Neck Lymph Node Metastasis Occurring Seven Years after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma].

A 59-year-old woman with pancreatic cancer underwent pancreaticoduodenectomy. The tumor was histologically diagnosed as a well-differentiated tubular adenocarcinoma with a small amount of mucinous component. After resection, the patient underwent hepatic perfusion therapy using 5-FU and gemcitabine chemotherapy for 1 year. 7 years after the initial surgery, CT and PET-CT revealed an isolated enlarged lymph node in the left neck. As the patient had no other metastasis, lymphadenectomy was performed. A diagnosis of lymph node metastasis originating from pancreatic cancer was confirmed on the basis of histological and immunohistopathological assessments. After the second resection, chemotherapy with S-1 was administered for 1 year. The patient has been alive without tumor relapse for 11 years. In patients with late recurrence after pancreatectomy, aggressive isolated lymph node resection and maintained chemotherapy may contribute to the improvement in prognosis.

[Mixed Type Liposarcoma with Intra-Abdominal Bleeding - Report of a Case].

A 71-year-old man presented with sudden abdominal pain. He had past history of atrial fibrillation, cerebral infarction and heart-valve replacement and received anticoagulant therapy with warfarin. Computed tomography of the abdomen revealed bloody ascites and a huge mass in contact with the third portion of the duodenum. The mass was encapsulated and consisted of a solid component with calcification and hematoma. Under the preoperative diagnosis of gastrointestinal stromal tumor with intra-abdominal bleeding, laparotomy was performed. Intraoperative findings revealed the tumor arising from the right mesocolon and excision of the tumor with right hemicolectomy was performed. Histologic examination confirmed a diagnosis of mixed type liposarcoma. No postoperative complication was observed and he was discharged home on the 8th postoperative day. He remains alive and well with no evidence of disease 52 months after resection.

[A Case of Hepatocellular Carcinoma with Lymph Node Metastasis Successfully Treated by Multidisciplinary Treatment].

Lymph node metastasis has a poor prognosis in patients with hepatocellular carcinoma(HCC). We report a case of HCC with lymph node metastasis successfully treated by multidisciplinary treatment. An 81-year-old woman who was followed up for liver cirrhosis received a diagnosis of HCC, which was detected by CT as a solitary tumor 20mm in diameter in the couinaud segment 7 of the liver. She underwent transcatheter arterial chemoembolization(TACE)twice for HCC because of her advanced age and no intention to undergo hepatectomy. Some 12 months later, local recurrence was managed by repeat TACE and paraaortic lymph node metastasis by surgical resection. The patient received radiotherapy for mediastinal nodal disease 6 months after the resection. She remains alive and well without no evidence of disease 84 months after the initial treatment. This case and a review of the literature suggest that multidisciplinary treatment with TACE, surgical resection and radiotherapy may provide a survival benefit for selected patients with HCC with isolated lymph node metastasis.

Ultra-dense spatial-division-multiplexed optical fiber transmission over 6-mode 19-core fibers.

Ultra-dense spatial-division multiplexing (SDM) is achieved by mode multiplexed technique with multiple cores in a single fiber, namely few-mode multi-core fiber. Using a 9.8-km six-mode nineteen-core fiber, we demonstrate an ultra-dense SDM transmission of 16-channels wavelength-division-multiplexed (WDM) dual-polarization quadrature phase shift keying signals, achieving a record spatial multiplicity of 114. With the help of ultra-dense Super-Nyquist WDM techniques in the 4.5-THz bandwidth of the full C-band, we demonstrate 2.05 Pbit/s transmission over 9.8-km six-mode nineteen-core fibers. In this experiment, the highest aggregate spectral efficiency of 456 bit/s/Hz is achieved.

DNA damage response and sphingolipid signaling in liver diseases.

Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.

[Resection for a Locally Advanced Duodenal Adenocarcinoma with Obstructive Jaundice and Hepatic and Pancreatic Invasion - A Case Report].

A 64-year-old woman diagnosed with duodenal adenocarcinoma with duodenal stenosis and obstructive jaundice was referred to our hospital. Computed tomography revealed a tumor measuring 9×6 cm in the second portion of the duodenum that had invaded the liver(S6)and head of the pancreas. After percutaneous transhepatic biliary drainage for obstructive jaundice, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy, partial resection of the liver(S6), and partial resection of the colon. Histologic examination showed the primary tumor to be moderately and poorly differentiated adenocarcinoma with hepatic and pancreatic invasion; lymph node metastasis was not found. The patient received S-1 for 1 year and remains alive and well with no evidence of disease 15 months after resection.

[Lymph Node Recurrence of Small Cell Carcinoma of the Extrahepatic Bile Ducts Effectively Treated with Cisplatin plus Irinotecan Chemotherapy - Report of a Case].

A 78-year-old man with jaundice was diagnosed with perihilar cholangiocarcinoma(Bismuth type I ). After endoscopic biliary drainage for jaundice, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Histologic examination and immunohistochemical staining with chromogranin A, synaptophysin, and CD56 resulted in a diagnosis of small cell carcinoma. Of the 18 dissected lymph nodes, 8 nodes contained a metastatic tumor. Left supraclavicular and paraaortic lymph node metastases were detected by computed tomography 5 months after the resection. He received cisplatin plus irinotecan chemotherapy, and after 2 courses of the chemotherapy, both metastatic lesions were reduced in size. He remains alive and well with no evidence of progressive disease after 6 courses of chemotherapy.

[Long-Term Survival after Reoperation for Lung Metastasis of Resected Pancreatic Adenocarcinoma - A Case Report].

A 66-year-old woman with pancreatic cancer underwent resection of the pancreatic body and tail. Thirty-seven months after the initial surgery, a tumor was found in S4 of the right lung, for which resection of the middle lobe of the lung was performed. A diagnosis of lung metastasis originating from pancreatic cancer was confirmed based on histological and immunohistopathological assessments. Sixty-seven months after the initial surgery, despite the gemcitabine-based adjuvant chemotherapy, a tumor was detected in S3 of the left lung, for which partial lung resection was performed. Similar to the previous diagnosis, the tumor was diagnosed as lung metastasis of pancreatic cancer on the basis of the pathological findings. After the third operation, despite gemcitabine and S-1 chemotherapy, widespread pulmonary metastasis developed. One hundred and thirty months after the initial surgery, the patient died of respiratory failure due to carcinomatous pleurisy.