Intensive locoregional therapy before Liver Transplantation for colorectal cancer liver metastasis: A novel pre-transplant protocol.

BACKGROUND: We describe a novel pre-liver-transplant (LT) approach in colorectal liver metastasis (CRLM) allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. METHODS: Patients undergoing LT for CRLM at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by PET scan and CEA. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. RESULTS: Nine patients received liver transplant out of 27 who were evaluated (33.3%). Median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease and four had treatment-induced cirrhosis. Pre-transplant management included chemotherapy (n=9) +/- Bevacizumab (n=6) and/or Anti-EGFR (n=6). Median pre-LT cycles of chemotherapy=16 (Range 10-40). Liver-directed therapy included Yttrium-90 (n=5), ablation (n=4), resection (n=4), and HAI-pump (n=3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n=6/8) and 60% (n=3/5). Recurrence occurred in the lungs (n=1), liver graft (n=1), and lungs+paraaortic nodes (n=1). Patients with pre-LT detectable disease had reduced RFS (p=0.04). All patients with recurrence had histologically-viable tumor in the liver explant. Patients treated in our protocol (n=16) demonstrated improved survival versus those who were not candidates (n=11) regardless of transplant status (p=0.01). CONCLUSION: A protocol defined by aggressive pre-transplant liver-directed treatment and transplant for patients with undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Update to 'A Contemporary Systematic Review on Liver Transplantation for Unresectable Liver Metastasis of Colorectal Cancer'.

Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.

Zero-field polarity-reversible Josephson supercurrent diodes enabled by a proximity-magnetized Pt barrier.

Simultaneous breaking of inversion and time-reversal symmetries in a conductor yields a non-reciprocal electronic transport1-3, known as the diode or rectification effect, that is, low (ideally zero) conductance in one direction and high (ideally infinite) conductance in the other. So far, most of the diode effects observed in non-centrosymmetric polar/superconducting conductors4-7 and Josephson junctions8-10 require external magnetic fields to break the time-reversal symmetry. Here we report zero-field polarity-switchable Josephson supercurrent diodes, in which a proximity-magnetized Pt layer by ferrimagnetic insulating Y3Fe5O12 serves as the Rashba(-type) Josephson barrier. The zero-field diode efficiency of our proximity-engineered device reaches up to ±35% at 2 K, with a clear square-root dependence on temperature. Measuring in-plane field-strength/angle dependences and comparing with Cu-inserted control junctions, we demonstrate that exchange spin-splitting11-13 and Rashba(-type) spin-orbit coupling13-15 at the Pt/Y3Fe5O12 interface are key for the zero-field giant rectification efficiency. Our achievement advances the development of field-free absolute Josephson diodes.

Enhanced Thermoelectric Power Factor in Carrier-Type-Controlled Platinum Diselenide Nanosheets by Molecular Charge-Transfer Doping.

2D transition metal dichalcogenides (TMDCs) have revealed great promise for realizing electronics at the nanoscale. Despite significant interests that have emerged for their thermoelectric applications due to their predicted high thermoelectric figure of merit, suitable doping methods to improve and optimize the thermoelectric power factor of TMDCs have not been studied extensively. In this respect, molecular charge-transfer doping is utilized effectively in TMDC-based nanoelectronic devices due to its facile and controllable nature owing to a diverse range of molecular designs available for modulating the degree of charge transfer. In this study, the power of molecular charge-transfer doping is demonstrated in controlling the carrier-type (n- and p-type) and thermoelectric power factor in platinum diselenide (PtSe2 ) nanosheets. This, combined with the tunability in the band overlap by changing the thickness of the nanosheets, allows a significant increase in the thermoelectric power factor of the n- and p-doped PtSe2 nanosheets to values as high as 160 and 250 µW mK-2 , respectively. The methodology employed in this study provides a simple and effective route for the molecular doping of TMDCs that can be used for the design and development of highly efficient thermoelectric energy conversion systems.

Crystallinity-dependent device characteristics of polycrystalline 2D n = 4 Ruddlesden-Popper perovskite photodetectors.

Ruddlesden-Popper (RP) perovskites have attracted a lot of attention as the active layer for optoelectronic devices due to their excellent photophysical properties and environmental stability. Especially, local structural properties of RP perovskites have shown to play important roles in determining the performance of optoelectronic devices. Here, we report the photodetector performance variation depending on the crystallinity of n = 4 two-dimensional (2D) RP perovskite polycrystalline films. Through controlling the solvent evaporation rate, 2D RP perovskite films could be tuned between highly- and randomly-orientated phases. We investigated how different factors related to the film crystallinity are reflected in the variation of photodetector performances by considering grain boundary and low energy edge state effects in n = 4 RP perovskites. Better understanding the interplay between these factors that govern the photophysical properties of the devices would be beneficial for designing high-performance RP perovskite-based optoelectronic devices.

Analysis of the interface characteristics of CVD-grown monolayer MoS2 by noise measurements.

We investigated the current-voltage and noise characteristics of two-dimensional (2D) monolayer molybdenum disulfide (MoS2) synthesized by chemical vapor deposition (CVD). A large number of trap states were produced during the CVD process of synthesizing MoS2, resulting in a disordered monolayer MoS2 system. The interface trap density between CVD-grown MoS2 and silicon dioxide was extracted from the McWhorter surface noise model. Notably, generation-recombination noise which is attributed to charge trap states was observed at the low carrier density regime. The relation between the temperature and resistance following the power law of a 2D inverted-random void model supports the idea that disordered CVD-grown monolayer MoS2 can be analyzed using a percolation theory. This study can offer a viewpoint to interpret synthesized low-dimensional materials as highly disordered systems.

Analysis of noise generation and electric conduction at grain boundaries in CVD-grown MoS2 field effect transistors.

Grain boundaries in a chemical vapour deposition (CVD)-grown monolayer of MoS2 induce significant effects on the electrical and low frequency noise characteristics of the MoS2. Here, we investigated the electrical properties and noise characteristics of MoS2 field effect transistors (FETs) made with CVD-grown monolayer MoS2. The electrical and noise characteristics of MoS2 FETs were analysed and compared for the MoS2 channel layers with and without grain boundaries. The grain boundary in the CVD-grown MoS2 FETs can be the dominant noise source, and dependence of the extracted Hooge parameters on the gate voltage indicated the domination of the correlated number-mobility fluctuation at the grain boundaries. The percolative noise characteristics of the single grain regions of MoS2 were concealed by the noise generated at the grain boundary. This study can enhance understanding of the electrical transport hindrance and significant noise generation by trapped charges at grain boundaries of the CVD-grown MoS2 devices.

Robotic versus laparoscopic left lateral sectionectomy of liver.

BACKGROUND: A few studies have reported only short-term outcomes of various robotic and laparoscopic liver resection types; however, published data in left lateral sectionectomy (LLS) have been limited. The aim of this study was to compare the long- and short-term outcomes of robotic and laparoscopic LLS. METHODS: We retrospectively compared demographic and perioperative data as well as postoperative outcomes of robotic (n = 12) and laparoscopic (n = 31) LLS performed between May 2007 and July 2013. Resection indications included malignant tumors (n = 31) and benign lesions (n = 12) including intrahepatic duct (IHD) stones (n = 9). RESULTS: There were no significant differences in perioperative outcomes of estimated blood loss, major complications, or lengths of stay, but operating time was longer in robotic than in laparoscopic LLS (391 vs. 196 min, respectively) and the operation time for IHD stones did not differ between groups (435 vs. 405 min, respectively; p = 0.190). Disease-free (p = 0.463) and overall (p = 0.484) survival of patients with malignancy did not differ between groups. The 2- and 5-year disease-free survival rates were 63.2 and 36.5 %, respectively. However, robotic LLS costs were significantly higher than laparoscopic LLS costs ($8183 vs. $5190, respectively; p = 0.009). CONCLUSIONS: Robotic LLS was comparable to laparoscopic LLS in surgical outcomes and oncologic integrity during the learning curve. Although robotic LLS was more expensive and time intensive, it might be a good option for difficult indications such as IHD stones.

Should Gastric Decompression be a Routine Procedure in Patients Who Undergo Pylorus-Preserving Pancreatoduodenectomy?

BACKGROUND: Nasogastric tube placement after abdominal surgery has been a standard procedure for many decades. In pancreatoduodenectomy, delayed gastric emptying (DGE) is still a leading postoperative complication, often resulting in patient anxiety or depression and prolonged hospital stays. Such complications have led many surgeons to prefer postoperative nasogastric decompression because of the greater risk of DGE. Therefore, the goal of this study was to evaluate the DGE and perioperative outcomes after pylorus-preserving pancreatoduodenectomy (PPPD) with or without routine gastrostomy. METHODS: From May 2009 to December 2014, 228 patients underwent PPPD at the Department of Surgery, Gangnam Severance Hospital, Yonsei University. The first cohort of 116 patients underwent surgery before June 2012 and uniformly underwent gastric decompression as a part of postoperative management. The second cohort of 112 patients underwent operation after July 2012, and gastric decompression was selectively used to facilitate exposure during operation and was removed in the operating room at the end of surgery. We evaluated DGE incidence, time to dietary tolerance, length of hospital stay, and postoperative gastric tube reinsertion rates. RESULTS: Gastric re-decompression was necessary in 38 patients (16.7 %), and there was a significant difference between the two groups (p = 0.006). Eleven (9.8 %) patients in the no-tube gastrostomy group required nasogastric tube reinsertion, and 27 (23.3 %) in the routine gastrostomy group required that the gastrostomy tube be re-drainage. There were no statistically significant differences in the frequency or severity of complications such as delayed gastric emptying or pancreatic leakage. CONCLUSIONS: Our study demonstrates that routine postoperative gastric decompression can be safely avoided in patients who undergo PPPD.

Correlation of Early Recurrence With In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Pancreas Cancer With Postoperative Gemcitabine Chemotherapy.

INTRODUCTION: Gemcitabine-based regimens represent the standard systemic first line treatment in patients after pancreatic resection. However, the clinical impact of gemcitabine varies significantly in individuals because of chemoresistance. An in vitro adenosine triphosphate based chemotherapy response assay (ATP-CRA) was designed to evaluate the sensitivity of cancer cells to various chemotherapeutic agents. This study investigated the correlation between in vitro gemcitabine sensitivity of tumor cells and early recurrence after curative resection. METHOD: From January 2007 to December 2010, the ATP-CRA for gemcitabine was tested in 64 patients surgically treated for pancreas cancer at Gangnam Severance Hospital, Seoul, Korea. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with pancreas cancer to predict disease-free survival (DFS) after curative resection in pancreas cancer. RESULT: The mean cell death rate (CDR) was 20.0 (±14.5) and divided into two groups according to the mean values of the CDR. Lymphovascular invasion was more frequently shown in gemcitabine resistance group without statistical significance. In univariate and multivariate analysis, advanced tumor stage and gemcitabine sensitive group (CDR ≥ 20) were identified as independent prognostic factors for DFS. CONCLUSIONS: Gemcitabine sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence following gemcitabine-based adjuvant chemotherapy in patients with pancreas cancer.

Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment.

BACKGROUND: We aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA). METHODS: One hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively. RESULTS: Univariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00pg/mL; hazard ratio [HR]=5.39; 95% confidence interval [CI]=1.27-22.93; P=0.022), low platelet count (<100×10(9)/L; HR=2.23; 95% CI=1.28-3.89; P=0.005), and low serum albumin level (⩽3.5g/L; HR=2.26; 95% CI=1.28-3.97; P=0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100×10(9)/L; HR=2.80; 95% CI=1.31-5.99; P=0.008) and multiple tumor (⩾2; HR=4.05; 95% CI=1.56-10.48; P=0.004) showed a negative prognostic impact on the overall survival. CONCLUSION: A low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.

The role of abdominal drainage to prevent of intra-abdominal complications after laparoscopic cholecystectomy for acute cholecystitis: prospective randomized trial.

BACKGROUND: Routine drainage of the abdominal cavity after surgery has been a robust dogma for many decades. Nevertheless, the policy of routine abdominal drainage is increasingly questioned. Many surgeons believe that routine drainage after surgery may prevent postoperative intra-abdominal infection. The goal of this study was to assess the role of drains in laparoscopic cholecystectomy (LC) for acute cholecystitis. MATERIALS AND METHODS: From May 2008 to July 2012, 160 patients that underwent LC due to acute cholecystitis at Gangnam Severance Hospital, Yonsei University Health System, Seoul, Korea, were enrolled in this study. After surgery, patients were randomly allocated to undergo drain placement in the subhepatic space (Group A) or no drainage (Group B). RESULTS: There was no significant difference in the intra-abdominal abscess rate, which was 0.0 % with Group A and 1.3 % with Group B (P = 0.319). The median subhepatic fluid collection was 4.1 mL (1.1­60 mL) in Group A and 4.5 mL (1.1­80.0 mL) in Group B (P = 0.298). However, the median hospital stay was 2 days (1­4 days) in Group B and 3 days (2­7 days) in group A (P = 0.001). The subgroup of empyema patients did not have any significant differences in intra-abdominal fluid collection or intra-abdominal abscess rate. CONCLUSIONS: This study suggests that postoperative routine drainage of the abdominal cavity for acute cholecystitis does not prevent intra-abdominal infections.

Intrinsic supercurrent non-reciprocity coupled to the crystal structure of a van der Waals Josephson barrier.

Non-reciprocal electronic transport in a spatially homogeneous system arises from the simultaneous breaking of inversion and time-reversal symmetries. Superconducting and Josephson diodes, a key ingredient for future non-dissipative quantum devices, have recently been realized. Only a few examples of a vertical superconducting diode effect have been reported and its mechanism, especially whether intrinsic or extrinsic, remains elusive. Here we demonstrate a substantial supercurrent non-reciprocity in a van der Waals vertical Josephson junction formed with a Td-WTe2 barrier and NbSe2 electrodes that clearly reflects the intrinsic crystal structure of Td-WTe2. The Josephson diode efficiency increases with the Td-WTe2 thickness up to critical thickness, and all junctions, irrespective of the barrier thickness, reveal magneto-chiral characteristics with respect to a mirror plane of Td-WTe2. Our results, together with the twist-angle-tuned magneto-chirality of a Td-WTe2 double-barrier junction, show that two-dimensional materials promise vertical Josephson diodes with high efficiency and tunability.

P16 hypermethylation predicts surgical outcome following curative resection of mid/distal bile duct cancer.

BACKGROUND: Bile duct cancer has very poor prognosis. Important prognostic factors include the TNM stage, cell differentiation, and histologic type; however, we often observe patients whose prognosis is not consistent with the TNM stage. Additional prognostic indicators are mandatory to complement those used presently. We evaluated the hypermethylation status of genes for the power to predict overall survival following curative resection of mid/distal bile duct cancer. METHODS: Pyrosequencing hypermethylation status at the loci of interest was analyzed in 65 mid/distal bile duct carcinoma specimens obtained at Severance Hospital of Yonsei University College of Medicine from January 2000 to December 2006. RESULTS: Significant methylation frequencies (MtI >5 %) were obtained for 5 genes (which P16 [17 %], DAPK [54 %], E-cadherin [60 %], RASSF-1 [46.2 %], and hMLH1 [43.1 %]). MtI status of P16, DAPK, and RASSF-1 were correlated with perineural invasion, tumor depth, and age, respectively. In the multivariate analysis of overall survival, the presence of lymph node metastasis and P16 methylation status were identified as independent prognostic factors for overall survival. Patients with unmethylated of P16 had the 3- and 5-year survival rates of 60.8 and 54.9 %, respectively. In patients with hypermethylated P16, the 3- and 5-year survival rates were 27.3 and 0.0 %, respectively. CONCLUSIONS: P16 hypermethylation and lymph node metastasis may predict overall survival in curative resected mid/distal bile duct cancer. Classification of mid/distal bile duct cancer by both genetic and epigenetic profiles may improve the accuracy in predicting outcome and the effectiveness of tailored therapy in these diseases.

Novel method of stent insertion for malignant lower rectal obstruction with proximal releasing delivery system (with video).

BACKGROUND: Self-expandable metal stents are an alternative to preoperative and palliative colostomy for patients with malignant colorectal obstruction. However, self-expandable metal stent placement is considered unsuitable or contraindicated for patients with malignant lower rectal obstruction within 5 cm of the anal verge because the exposed stent portion can irritate the distal rectum and cause anal pain and a foreign body sensation. OBJECTIVE: To describe our experience with 6 patients with malignant lower rectal obstruction who underwent stent insertion with a proximal releasing delivery system (PRDS). DESIGN: Prospective clinical series outcome study. SETTING: A tertiary-care referral university hospital. PATIENTS: This study involved all patients at our center who had a malignant lower rectal obstruction within 5 cm of the anal verge caused by rectal cancer and bladder cancer. INTERVENTION: Uncovered stent with the PRDS with endoscopic and fluoroscopic guidance. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rate, adverse event rate, and stent migration rate. RESULTS: All stents were placed at the expected location. Technical and clinical success rates were 100%. Two patients reported anal pain, which was controlled with analgesics. One case of tumor ingrowth occurred after 5 months and was treated with reinsertion of a stent with the PRDS. After stent insertion, the patients received chemotherapy, chemoradiotherapy, or conservative care. LIMITATIONS: Small number of patients and no comparison group. Further prospective, randomized, controlled trials are needed. CONCLUSIONS: Uncovered stent insertion with the PRDS is a feasible, safe, and effective treatment for the patient with malignant lower rectal obstruction within 5 cm from the anal verge.

Drainage volume after pancreaticoduodenectomy is a warning sign of chyle leakage that inversely correlates with a diagnosis of pancreatic fistula.

BACKGROUND: Chyle leakage is a rare complication of pancreaticoduodenectomy (PD), and its association with pancreatic fistula has not been established. The aim of this study was to (1) evaluate the incidence, management, and risk factors of chyle leakage after PD; (2) determine if there is a relation between chyle leakage and diagnosis of pancreatic fistula; and (3) predict chyle leakage with drainage volume early. METHODS: A total of 222 patients underwent PD or pylorus-preserving PD. We used the clinical database registry system of the Gangnam Severance Hospital, Yonsei University Health System to establish a retrospective cohort with clinicopathologic data. RESULTS: Altogether, 24 patients (10.8 %) developed chyle leakage. Chyle leakage was identified at a median 5 days after surgery and a mean 2 days after enteral intake. The mean drain triglyceride level was 315 mg/dl. Early enteral intake was independently associated with chyle leakage. Chyle leakage was inversely correlated with a diagnosis of pancreatic fistula with marginal significance (odds ratio 0.27; 95 % confidence interval 0.66-1.09). The receiver operating characteristic curve of the volume on postoperative day 4 demonstrated an area under the curve of 0.740 (p = 0.0001). Drainage >335 ml indicated possible chyle leakage. CONCLUSIONS: Chyle leakage after PD is associated with early enteral intake. It was inversely correlated with a diagnosis of pancreatic fistula because of the dilution effect of drainage volume on the concentration of drained amylase. Because early diagnosis helps with appropriate management, prediction/suspicion of chyle leakage based on drainage volume may be useful.

Can we predict postoperative pancreatic leakage after pancreaticoduodenectomy using preoperative fecal elastase-1 level?

INTRODUCTION: The measurement of fecal elastas-1 in stools is a sensitive and relatively inexpensive noninvasive test. The aim of this study was to study fecal elastase levels in patients who develop pancreatic leakage after pancreaticoduodenectomy (PD) to determine if fecal elastase level can be used to predict patients at high risk for pancreatic leakage after PD. METHODS: Pancreatic function was considered normal when fecal elastase-1 concentration exceeded 200 µg/g feces and moderately or severely insufficient when fecal elastas-1 concentration was less than 200 µg/g feces. RESULTS: Of 123 patients who underwent PD, 67 (54.5%) showed fecal elastase-1 levels less than 200 µg/g, indicating moderate or severe pancreatic insufficiency. Pancreas texture, pathology origin, and level of γ-glutamyl transferase (r-GT) were significantly correlated with fecal elastas-1 level. On univariate analysis, the incidence of pancreatic leakage was significantly greater in the group with normal fecal elastase-1 level (≥200 µg/g), pathologic origin (bile duct/ampulla/duodenum), and soft pancreas texture. In multivariate analysis, normal fecal elastase-1 level (≥200 µg/g) and soft pancreatic texture were identified as independent factors for pancreatic leakage. CONCLUSIONS: Fecal elastase-1 is the most simple and objective method for predicting pancreatic leakage after PD.

Chiral antiferromagnetic Josephson junctions as spin-triplet supercurrent spin valves and d.c. SQUIDs.

Spin-triplet supercurrent spin valves are of practical importance for the realization of superconducting spintronic logic circuits. In ferromagnetic Josephson junctions, the magnetic-field-controlled non-collinearity between the spin-mixer and spin-rotator magnetizations switches the spin-polarized triplet supercurrents on and off. Here we report an antiferromagnetic equivalent of such spin-triplet supercurrent spin valves in chiral antiferromagnetic Josephson junctions as well as a direct-current superconducting quantum interference device. We employ the topological chiral antiferromagnet Mn3Ge, in which the Berry curvature of the band structure produces fictitious magnetic fields, and the non-collinear atomic-scale spin arrangement accommodates triplet Cooper pairing over long distances (>150 nm). We theoretically verify the observed supercurrent spin-valve behaviours under a small magnetic field of <2 mT for current-biased junctions and the direct-current superconducting quantum interference device functionality. Our calculations reproduce the observed hysteretic field interference of the Josephson critical current and link these to the magnetic-field-modulated antiferromagnetic texture that alters the Berry curvature. Our work employs band topology to control the pairing amplitude of spin-triplet Cooper pairs in a single chiral antiferromagnet.