Laparoscopic liver resection for a patient of hepatocellular carcinoma with von Willebrand disease: a case report.

BACKGROUND: The safety of laparoscopic hepatectomy for inherited coagulation disorders is unclear; however, the safety of open hepatectomy has been reported in several studies. Herein, we report the first case of a laparoscopic hepatectomy for a patient with von Willebrand Disease (VWD). CASE PRESENTATION: A 76-year-old male with a history of chronic hepatitis C and VWD type 2B was advised surgical resection of a 4 cm hepatocellular carcinoma in segment 7 of the liver. The patient was diagnosed with VWD in his 40 s due to gastrointestinal bleeding caused by gastric erosion. The von Willebrand factor (VWF) ristocetin cofactor activity was 30%, and VWF large multimer deficiency and increased ristocetin-induced platelet agglutination were observed. The preoperative platelet count was reduced to 3.5 × 104/µL; however, preoperative imaging findings had no evidence of liver cirrhosis, such as any collateral formations and splenomegaly. The indocyanine green retention rate at 15 min was 10%, and his Child-Pugh score was 5 (classification A). Perioperatively, VWF/factor VIII was administered in accordance with our institutional protocol. A laparoscopic partial hepatectomy of the right posterior segment was performed. The most bleeding during surgery occurred during the mobilization of the right lobe of the liver due to inflammatory adhesion between the retroperitoneum and the tumor. Bleeding during parenchymal transection was controlable. The duration of hepatic inflow occlusion was 65 min. The surgical duration was 349 min, and the estimated blood loss was 2150 ml. Four units of red blood cells and fresh frozen plasma were transfused at the initiation of parenchymal transection, and 10 units of platelets were transfused at the end of the parenchymal transection. On postoperative day 1, the transection surface drainage fluid became hemorrhagic, and emergency contrast-enhanced computed tomography showed extravasation in the greater omentum. Percutaneous transcatheter arterial embolization of the omental branch of the right gastroepiploic artery was performed. No further postoperative interventions were required. The patient was discharged on postoperative day 14. CONCLUSION: The indications for laparoscopic hepatectomy in patients with VWD should be carefully considered, and an open approach may still be the standard approach for patients with VWD.

Impact of tumor proximity to vessel on conversion in laparoscopic liver resection: A retrospective cohort study.

BACKGROUND: Although various difficulty scoring systems have been proposed for laparoscopic liver resection (LLR), details remain uncertain regarding distance between the tumor and vessels as a factor of difficulty. We aimed to examine the risk factors for conversion to open hepatectomy in LLR, including distance between tumor and vessels. METHODS: Between January 2012 and December 2022, 118 patients who underwent LLR were retrospectively enrolled and their perioperative characteristics were evaluated. RESULTS: A total of 10 cases (8.5%) were converted to open hepatectomy during LLR. The conversion group had lower platelet count, shorter distance between the tumor and a medium vessel (defined as diameter of 5-10 mm), and greater tumor depth compared with the pure LLR group. Receiver-operating characteristic curve analysis identified 10 mm as the optimal cutoff value of tumor proximity to a medium vessel (sensitivity, 80.0%, specificity, 78.7%, AUC 0.817) for predicting conversion. In multivariate analysis, lower platelet count (p = .028) and tumor proximity within 10 mm to a medium vessel (p = .001) were independent risk factors for conversion in LLR. CONCLUSIONS: Our study suggests tumor proximity within 10 mm to a medium vessel and lower platelet count as predictors of unfavorable intraoperative conversion in LLR.

A Rare Presentation of Lymph Node Metastasis of VIPoma After Three Years of Resection: A Case Report.

Vasoactive intestinal peptide-producing tumor of the pancreas (VIPoma) is one of the rarer subtypes of neuroendocrine tumor (NET) of the pancreas. It usually represents intractable diarrhea, weight loss, and electrolyte abnormalities secondary to diarrhea. The most common site of metastasis of VIPoma is the liver. Furthermore, lymph node metastasis (LNM) is rare, and no metachronous LNM with a resectable situation has been reported before. A 60-year-old male patient (height: 181 cm, body weight: 74 kg) with a history of operated pancreatic VIPoma three years ago was referred to our department due to the detection of lymphadenomegaly which was suggestive of lymph node metastasis by routine follow-up computed tomography (CT). Preoperative CT showed a lymph node on the left side of the abdominal aorta and caudal side of the left renal vein with a size of 1 cm. Lymphadenectomy was performed without significant complications and blood loss. This is the first report of metachronous LNM in a patient with operated VIPoma. Although much rarer than solid organ metastasis of VIPoma, LNM in these patients can also be seen synchronously and metachronously. Close follow-up and vigilance are key to preventing recurrence-related morbidity and mortality in these patients.

C-Reactive Protein-to-Albumin Ratio to Predict Tolerability of S-1 as an Adjuvant Chemotherapy in Pancreatic Cancer.

Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs.

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

PURPOSE: Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. METHODS: We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. RESULTS: Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). CONCLUSION: Prolonged WIT is associated with intractable PBS following LDLT.

Albumin-indocyanine green evaluation of future liver remnant predicts liver failure after anatomical hepatectomy for hepatocellular carcinoma: A dual-center retrospective study.

Aim: The albumin-indocyanine green evaluation (ALICE) score is a useful predictor of post-hepatectomy liver failure (PHLF); however, its usefulness in combination with future liver remnant (FLR), measured by 3-D volumetry, has not been investigated. This study aimed to investigate the relationship between the ALICE of the FLR (ALICE-FLR) score and severe PHLF. Methods: The clinical data of 215 patients who underwent anatomical hepatectomy for hepatocellular carcinoma without portal vein embolization at two institutes between January 2010 and December 2021 were analyzed retrospectively. PHLF occurrence and severity were determined according to the International Study Group of Liver Surgery's definition. Grades B and C PHLF were defined as severe PHLF. The ALICE-FLR, ALICE scores, and indocyanine green clearance of FLR (ICGK-FLR) were evaluated for severe PHLF prediction. Results: Severe PHLF was observed in 40 patients (18.6%). The areas under the curve (AUCs) for the ALICE-FLR, ALICE scores, ICGK-FLR, and FLR were 0.76, 0.64, 0.73, and 0.69, respectively. The AUC of the ALICE-FLR score was significantly higher than that of the ALICE score. The ALICE-FLR score was identified as an independent predictor of severe PHLF (the odds ratio for every 0.01 increment in the ALICE-FLR score was 1.24; 95% confidence interval, 1.070-1.453; p = 0.004). Among patients with severe PHLF, the ALICE-FLR score was significantly higher in the grade C than in the grade B PHLF group. Conclusion: The combination of liver function models, including indocyanine green, albumin, and FLR is considered compatible for predicting severe PHLF.

Dorsal approach in laparoscopic extended left hemi-hepatectomy: A case series.

RATIONALE: The utility of the dorsal approach has been reported for laparoscopic left hemi-hepatectomy. PATIENT CONCERNS: The aim of the present study is to show the usefulness of the dorsal approach for laparoscopic extended left-hemi-hepatectomy while ensuring safe identification of hepatic veins and dissection of the dorsal tumor margin. DIAGNOSES: Tumors requiring extended left hemi-hepatectomy. INTERVENTIONS: After mobilization of the lateral sector and division of the Arantius plate, parenchyma above the Arantius plate is removed to expose the root of the middle hepatic vein and left hepatic vein. Each of these veins can be isolated separately either intra- or extra-hepatically. After removing the parenchyma on the cranial side of the left Glissonean pedicle continuous with the exposed hepatic veins, the left Glissonean pedicle is isolated using the Glissonean pedicle transection method. After division of the left hepatic vein and Glissonean pedicle, segment 4 (in which the main part of the tumor is commonly located) is dissected from the anterior plane of the paracaval portion of the caudate lobe by the dorsal approach, along with the hepatic hilum. Following dissection of the dorsal side of the tumor, and division of parenchyma from the anterior edge of the liver, the anterior Glissonean branches and middle hepatic vein are divided safely and the specimen is resected. OUTCOMES: Three patients underwent laparoscopic extended left hemi-hepatectomy, with no open conversions. Operative time and blood loss were 331 (concomitant with another partial hepatectomy), 277, and 315 minutes; and 200, 100, and 100 g, respectively. The postoperative courses were uneventful. LESSONS: The dorsal approach maximizes the advantages of laparoscopic extended left hemi-hepatectomy and can be performed safely.

Novel embryological classifications of hepatic arteries based on the relationship between aberrant right hepatic arteries and the middle hepatic artery: A retrospective study of contrast-enhanced computed tomography images.

BACKGROUND: Variations in hepatic arteries are frequently encountered during pancreatoduodenecomy. Identifying anomalies, especially the problematic aberrant right hepatic artery (aRHA), is crucial to preventing vascular-related complications. In cases where the middle hepatic artery (MHA) branches from aRHAs, their injury may lead to severe liver ischemia. Nevertheless, there has been little information on whether MHA branches from aRHAs. This study aimed to investigate the relationship between aRHAs and the MHA based on the embryological development of visceral arteries. METHODS: This retrospective study analyzed contrast-enhanced computed tomography images of 759 patients who underwent hepatobiliary-pancreatic surgery between January 2011 and August 2022. The origin of RHAs and MHA courses were determined using three-dimensional reconstruction. All cases of aRHAs were categorized into those with or without replacement of the left hepatic artery (LHA). RESULTS: Among the 759 patients, 163 (21.4%) had aRHAs. Five aRHAs patterns were identified: (Type 1) RHA from the gastroduodenal artery (2.7%), (Type 2) RHA from the superior mesenteric artery (SMA) (12.7%), (Type 3) RHA from the celiac axis (2.1%), (Type 4) common hepatic artery (CHA) from the SMA (3.5%), and (Type 5) separate branching of RHA and LHA from the CHA (0.26%). The MHA did not originate from aRHAs in Types 1-3, whereas in Type 4, it branched from either the RHA or LHA. CONCLUSIONS: Based on the developmental process of hepatic and visceral arteries, branching of the MHA from aRHAs is considered rare. However, preoperative recognition and intraoperative anatomical assessment of aRHAs is essential to avoid injury.

Impact of the inferior vena cava morphology on fluid dynamics of the hepatic veins.

We reported previously that a large vertical interval between the hepatic segment of the inferior vena cava (IVC) and right atrium (RA), referred to as the IVC-RA gap, was associated with more intraoperative bleeding during hemi-hepatectomy. We conducted a computational fluid dynamics (CFD) study to clarify the impact of fluid dynamics resulting from morphologic variations around the liver. The subjects were 10 patients/donors with a large IVC-RA gap and 10 patients/donors with a small IVC-RA gap. Three-dimensional reconstructions of the IVC and hepatic vessels were created from CT images for the CFD study. Median pressure in the middle hepatic vein was significantly higher in the large-gap group than in the small-gap group (P = 0.008). Differences in hepatic vein pressure caused by morphologic variation in the IVC might be one of the mechanisms of intraoperative bleeding from the hepatic veins.

Clamp-crushing Pancreatic Transection in Minimally Invasive Distal Pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy has become a widely accepted procedure for tumors located in the pancreatic body or tail. However, pancreatic transection by linear stapler is generally avoided for pancreatic body tumors located above the portal vein because the surgical margin width is narrowed after taking into account the cutting allowance for insertion of the stapling device. Herein, we report a parenchymal clamp-crushing procedure that provides a sufficient surgical margin in pancreatic transection. METHODS: Two patients with suspected early pancreatic cancer underwent pancreatic transection using the clamp-crushing procedure. The planned pancreatic transection line was set just to the left of the gastroduodenal artery in both cases. Robotic and laparoscopic distal pancreatectomy were performed in 1 patient each. Patients were positioned supine with split legs. Parenchymal transection was performed with crushing by VIO 3 (ERBE Elektromedizin) operated in softCOAG Bipolar mode with Effect 2/modulation 50. After crushing, remnant tissue was cut in autoCUT Bipolar mode operated by VIO 3 with Effect 2/modulation 50, or cut after secured by clipping. RESULTS: The surgical duration was 253 and 212 minutes, and estimated blood loss was 0 and 50 mL in the 2 patients, and both were discharged with uneventful courses. Pathologic examination confirmed a negative surgical margin in both patients. CONCLUSION: Clamp-crushing pancreatic transection for distal pancreatectomy might be a suitable treatment option for achieving sufficient surgical margin in pancreatic body tumors located close to the portal vein.

Diagnostic value of quantification of cell-free DNA for suspected gallbladder cancer.

Background and Aim: An accurate preoperative diagnosis as the basis for deciding the most appropriate surgical procedure is essential for patients with suspected gallbladder cancer (GBC). The aim of this study was to investigate the usefulness of cell-free DNA (cfDNA) for the preoperative detection of ≥T2 invasion in patients with suspected GBC. Methods: Twenty-four patients who underwent resection for suspected GBC were enrolled. The concentration of cfDNA obtained from blood samples preoperatively was measured and evaluated in two distributions. The first peak (less than 200 base pairs) of cfDNA distribution was defined as the shorter fragment cfDNA, considered to originate mainly from apoptosis; and the second peak (200 base pairs or more) was defined as the longer fragment cfDNA, originating mainly from necrosis. Results: Pathological analysis identified benign disease in 12 patients and GBC in 12 patients, of whom 6 patients had ≥pT2 GBC. Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 were significantly higher in the ≥pT2 GBC group than in the benign/

Geriatric Nutritional Risk Index Predicts Tolerability of S-1 as Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Surgery plus adjuvant chemotherapy (AC) for resectable pancreatic ductal adenocarcinoma (PDAC) has been shown to prolong survival compared with surgery alone. Thus, it is of clinical importance that these patients receive a continuous dose of S-1. The aim of this study was to examine whether the geriatric nutritional risk index (GNRI) is a predictor for the completion of S-1 as AC for PDAC. METHODS: Seventy-seven patients who were administered S-1 as AC after pancreatectomy for PDAC between January 2010 and October 2021 were retrospectively enrolled. Predictive markers were statistically analyzed for S-1 completion, which was defined as continued oral administration with relative dose intensity of >80%. RESULTS: Patients were divided into the S-1 complete group (n = 55; 71.4%) and S-1 incomplete group (n = 22; 28.6%). There was a significant association of higher GNRI ( P = 0.013) at the onset of AC with the completion of S-1. Receiver operating characteristic curve analysis revealed 94.4 as the optimal cutoff value of GNRI for predicting the completion of S-1. Univariate and multivariate analyses confirmed that GNRI >94.4 was independently associated with the completion of S-1 ( P = 0.007). CONCLUSIONS: High GNRI value is a predictive marker for the completion of S-1 as AC for PDAC.

Living Donor Liver Transplantation in Patients with Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies Using Preoperative Desensitization Therapy According to Intensity of Donor-Specific Antibodies: A Single-Center Study.

BACKGROUND In liver transplantation (LT), preoperative desensitization therapy is considered necessary in patients positive for donor-specific anti-human leukocyte antigen antibodies (DSAs). However, the relationship between DSA intensity and the necessary desensitization therapy is unclear. MATERIAL AND METHODS A total of 37 adult living donor (LD) LTs performed between January 2016 and March 2022 were examined. Mycophenolate mofetil (MMF) was administered preoperatively in DSA-positive cases with positive lymphocyte cross-matching who underwent LDLT. In those with strongly positive DSA (mean fluorescence intensity 10 000), rituximab was administered 2 weeks before LDLT in addition to MMF. Cross-reactive epitope group antigen (CREG)-alone-positive cases were also treated with preoperative MMF when lymphocyte cross-matching was positive. RESULTS Of the 37 patients, 9 were DSA-positive, 7 were CREG-alone-positive, and the others were double-negative. Of 9 DSA-positive cases, desensitization therapy was performed in 7, among which rituximab administration was performed in 3 strongly DSA-positive cases. Of 7 CREG-alone-positive cases, 2 were lymphocyte cross-match-positive and underwent desensitization therapy. The 1-year survival rate was 100% in both DSA- and CREG-alone-positive cases. The frequency of T-cell mediated rejection in DSA-positive, CREG-alone-positive, and double-negative cases was 22%, 43%, and 29%, respectively, with no significant difference. Antibody-mediated rejection occurred in only 1 patient, who was strongly DSA-positive and blood-group incompatible. There was also no significant difference among the 3 groups in terms of the frequency of biliary complications or 90-day mortality. CONCLUSIONS Satisfactory LDLT results were achieved in DSA- and CREG-alone-positive cases following desensitization therapy.

Epstein-Barr Virus-Associated Latent Malignant Lymphoma With Acute Exacerbation After Living Donor Liver Transplantation: Case Report.

Concomitant malignant lymphoma at the time of transplantation is usually considered a contraindication to liver transplantation (LT). We report a case of Epstein-Barr virus (EBV)-associated malignant lymphoma that was latent preoperatively and rapidly became aggravated after LT. A 69-year-old man was referred to our hospital with an exacerbation of abdominal distension due to polycystic liver. As cystic infection, ascites, and deteriorated liver reserve function occurred after hepatic artery embolization, he underwent living-donor LT with his daughter as the donor. His respiratory condition worsened, and he was moved to the intensive care unit on postoperative day 34. Histopathologic examination of the excised liver returned around the same time revealed findings suggestive of EBV-associated malignant lymphoma in lymph nodes near the gallbladder. Subsequent computed tomography scans showed apparent neoplastic lesions in the abdominal cavity and worsening pleural effusion and ascites. Numerous atypical lymphocytes were observed in the pleural effusion and ascites, and the patient was diagnosed with exacerbation of EBV-associated malignant lymphoma. He was treated unsuccessfully with rituximab and died 66 days after LT. Caution should be exercised in elderly immunocompromised transplant candidates who may have comorbid EBV-associated lymphoproliferative disease.

Early Postoperative Varicella-Zoster Virus Encephalitis After Adult ABO-Incompatible Living Donor Liver Transplantation: A Case Report.

There have never been any reports of adult varicella-zoster virus (VZV) encephalitis cases. Here, we report a case of VZV encephalitis after adult ABO-incompatible living donor liver transplantation (LDLT). A 38-year-old man with decompensated liver cirrhosis caused by the hepatitis C virus was referred to our hospital as an LDLT candidate. Rituximab was administered 3 weeks before the operation, and immunosuppression agents were administered 1 week before the LDLT. Plasma exchange was performed 3 times before the LDLT. The right lobe from his mother's liver was used for the ABO-incompatible LDLT. On postoperative day (POD) 9, vascular stenting for intraabdominal bleeding from the common hepatic artery was performed by interventional radiology and was followed by re-laparotomy for abdominal drainage of the hematoma. However, there were various degrees of continued bleeding thereafter. On POD 12, due to a convulsion seizure with loss of consciousness, the patient was started on anticonvulsant therapy. On POD 15, there was an increased frequency of convulsion attacks and a prolonged loss of consciousness. A lumbar puncture was performed on POD 20 due to the appearance of shingles. The positive polymerase chain reaction of the VZV-DNA from the cerebrospinal fluid was detected, and he was diagnosed with VZV encephalitis. He rapidly regained alertness, and there were no further observed convulsion attacks after administration of a steroid pulse and acyclovir. Brain magnetic resonance imaging performed on 2 subsequent postoperative months showed findings that matched with VZV encephalitis. He was discharged as he had recovered and was ambulatory 3 months after LDLT.

The impact of cystic duct tube on the onset time of postoperative bile leakage after hepatectomy: A propensity score-matched analysis.

BACKGROUND: The cystic duct tube (C-tube) was used to reduce bile leakage (BL) incidence after hepatectomy. Nevertheless, delayed BL is sometimes experienced even using C-tube. This study investigates the impact of C-tube use on the onset time of post-hepatectomy BL. METHODS: Data from 455 consecutive patients who underwent hepatectomy without biliary reconstruction between November 2007 and July 2020 were analyzed retrospectively. A C-tube was used for intraoperative biliary injury or in consideration of BL risk. BL was divided into two groups according to the postoperative onset time: early onset and late onset. To assess the association between C-tube use and BL, propensity score matching in a 1:1 ratio was performed to match BL risk factors between the C-tube and no-C-tube groups. RESULTS: BL occurred in 30 (6.6%) of the 455 included patients. C-tubes were used in 51 patients (11.2%) with open hepatectomy, high-risk hepatectomy, massive blood loss, long operation time, or prophylactic drain placement. After propensity score matching, BL occurred in 17 of 102 patients (16.7%). Early-onset BL occurred significantly less frequently in the C-tube group than in the no-C-tube group (3.9% vs. 15.7%, p = 0.046); however, late-onset BL was more common in the C-tube group (9.8% vs. 3.9%, p = 0.24). Six of seven patients (85.7%) with BL with C-tube use developed BL after C-tube removal. CONCLUSION: C-tube drainage may reduce early-onset BL in cases having risk factors for BL. Conversely, since late-onset BL often occurs after C-tube removal, attention should be paid to those cases.

Simple Symptom-Based Prediction of COVID-19: A Single-Center Study of Outpatient Fever Clinic in Japan.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) symptoms are not fully understood in non-hospitalized individuals in Japan, and COVID-19 differentiation by symptoms alone remained challenging. Therefore, this study aimed to examine COVID-19 prediction from symptoms using real-world data in an outpatient fever clinic. METHODS: We compared the symptoms of COVID-19-positive and negative patients who visited the outpatient fever clinic at Imabari City Medical Association General Hospital and tested for COVID-19 from April 2021 to May 2022. This retrospective single-center study enrolled 2,693 consecutive patients. RESULTS: COVID-19-positive patients had a higher frequency of close contact with COVID-19-infected patients compared with COVID-19-negative patients. Moreover, patients with COVID-19 had high-grade fever at the clinic compared with patients without COVID-19. Additionally, the most common symptom in patients with COVID-19 was sore throat (67.3%), followed by cough (62.0%), which was approximately twice as common in patients without COVID-19. COVID-19 was more frequently identified in patients having a fever (≥37.5℃) with a sore throat, a cough, or both. The positive COVID-19 rate reached approximately half (45%) when three symptoms were present. CONCLUSION: These results suggested that COVID-19 prediction by combinations of simple symptoms and close contact with COVID-19-infected patients might be useful and lead to recommendations for testing of COVID-19 in symptomatic individuals.

Prognostic Role of the Intrahepatic Lymphatic System in Liver Cancer.

Although several prognosticators, such as lymph node metastasis (LNM), were reported for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the prognostic impact of intrahepatic lymphatic vessel invasion (LVI) in liver cancer has rarely been reported. We sought to clarify the prognostic impact of intrahepatic lymphatic system involvement in liver cancer. We systematically reviewed retrospective studies that described LVI and clinical outcomes of liver cancer and also included studies that investigated tumor-associated lymphangiogenesis. We conducted a meta-analysis using RevMan software (version 5.4.1; Cochrane Collaboration, Oxford, UK). The prognostic impact of intrahepatic LVI in HCC was not reported previously. However, tumor-associated lymphangiogenesis reportedly correlates with prognosis after HCC resection. The prognostic impact of intrahepatic LVI was reported severally for ICC and a meta-analysis showed that overall survival was poorer in patients with positive LVI than with negative LVI after resection of ICC. Lymphangiogenesis was also reported to predict unfavorable prognosis in ICC. Regarding colorectal liver metastases, LVI was identified as a poor prognosticator in a meta-analysis. A few reports showed correlations between LVI/lymphangiogenesis and LNM in liver cancer. LVI and lymphangiogenesis showed worse prognostic impacts for liver cancer than their absence, but further study is needed.

Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer.

Despite extensive research, pancreatic cancer remains a lethal disease with an extremely poor prognosis. The difficulty in early detection and chemoresistance to therapeutic agents are major clinical concerns. To improve prognosis, novel biomarkers, and therapeutic strategies for chemoresistance are urgently needed. microRNAs (miRNAs) play important roles in the development, progression, and metastasis of several cancers. During the last few decades, the association between pancreatic cancer and miRNAs has been extensively elucidated, with several miRNAs found to be correlated with patient prognosis. Moreover, recent evidence has revealed that miRNAs are intimately involved in gemcitabine sensitivity and resistance through epithelial-to-mesenchymal transition, the tumor microenvironment, and drug metabolism. Gemcitabine is the gold standard drug for pancreatic cancer treatment, but gemcitabine resistance develops easily after chemotherapy initiation. Therefore, in this review, we summarize the gemcitabine resistance mechanisms associated with aberrantly expressed miRNAs in pancreatic cancer, especially focusing on the mechanisms associated with epithelial-to-mesenchymal transition, the tumor microenvironment, and metabolism. This novel evidence of gemcitabine resistance will drive further research to elucidate the mechanisms of chemoresistance and improve patient outcomes.