Rescue of outflow block of the remnant left liver after extended right hemihepatectomy for resection of a tumor in the caudate lobe.

Outflow block of the liver is a life-threatening event after living donor liver transplantation. Herein, we rescued a patient suffering from the outflow block of the remnant left hemiliver caused by bending of the left hepatic vein (LHV) after right hemihepatectomy plus caudate lobectomy combined with resection of the middle hepatic vein (MHV). A metastatic tumor sized 6 cm in the caudate lobe of the liver involving the root of the MHV was found in a 50's year old patient after resection of a right breast cancer eight years ago. Right hemihepatectomy and caudate lobectomy combined with resection of the MHV was performed using a two-stage hepatectomy (partial TIPE ALPPS). On day 1, the total bilirubin value increased to 4.5 mg/dL, and a dynamic computed tomography (CT) scan showed the bent LHV. On the diagnosis of outflow block of the left liver, a self-expandable metallic stent was placed in the LHV using an interventional approach, and the pressure in the LHV decreased from 27 cmH2O to 12 cmH2O. The bilirubin value decreased to 1.2 mg/dL on day 3. Outflow block of the LHV can happen after extended right hemihepatectomy with resection of the MHV. Early diagnosis and interventional stenting treatment can rescue the patient from congestive liver failure.

Trends in the treatment of advanced pancreatic cancer.

Pancreatic cancer (PC) has the poorest prognosis among digestive cancers; only 15-20% of cases are resectable at diagnosis. This review explores multidisciplinary treatments for advanced PC, emphasizing resectability classification and treatment strategies. For locally advanced unresectable PC, systemic chemotherapy using modified FOLFIRINOX and gemcitabine with albumin-bound paclitaxel is standard, while the role of chemoradiation is debated. Induction chemotherapy followed by chemoradiation may be a promising therapy. Conversion surgery after initial chemotherapy or chemoradiotherapy offers favorable survival, however criteria for conversion need further refinements. For metastatic PC, clinical trials using immune checkpoint inhibitors and molecular targeted therapies are ongoing. Multidisciplinary approaches and further research are crucial for optimizing treatment and improving outcomes for advanced PC.

Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma.

Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01-2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31-6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner.

Impact of biliary drainage method before pancreaticoduodenectomy on short- and long-term outcomes in patients with periampullary carcinoma and obstructive jaundice: A multicenter retrospective analysis.

BACKGROUND: The optima preoperative biliary drainage before pancreaticoduodenectomy in patients with biliary tract and pancreatic cancer remains controversial. METHODS: A total of 898 patients who underwent preoperative biliary drainage via endoscopic retrograde biliary drainage, endoscopic transnasal biliary drainage, or percutaneous transhepatic biliary drainage before pancreaticoduodenectomy for biliary tract and pancreatic cancer were included. Perioperative and long-term outcomes were analyzed. RESULTS: The Clavien-Dindo grade ≥3 morbidity rates after pancreaticoduodenectomy were higher in the endoscopic retrograde biliary drainage (21.9%; P = .001) or endoscopic transnasal biliary drainage (20.2%; P = .007) than in the percutaneous transhepatic biliary drainage (9.7%) groups. In biliary tract cancer, the frequency of dissemination after pancreaticoduodenectomy was higher in the percutaneous transhepatic biliary drainage (15.3%) than in the endoscopic retrograde biliary drainage (0.7%; P = .001) and endoscopic transnasal biliary drainage (4.1%; P = .037) groups; percutaneous transhepatic biliary drainage was an independent factor associated with worse disease-free survival (P = .04), whereas in pancreatic cancer the frequency of dissemination and survival was comparable among the 3 preoperative biliary drainage methods. Albumin <3.9 g/dL was independently associated with worse overall survival in patients with both pancreatic (P = .038) and biliary tract (P = .002) cancers, respectively. During biliary drainage, external drainage (P = .038) was independently associated with albumin <3.9 g/dL; albumin was higher in endoscopic retrograde biliary drainage group than in endoscopic transnasal biliary drainage or percutaneous transhepatic biliary drainage groups after 21 days from tube insertion. CONCLUSION: In biliary tract cancer, percutaneous transhepatic biliary drainage may carry the risk of increasing the incidence of disseminative recurrence. In pancreatic cancer, percutaneous transhepatic biliary drainage is preferable owing to fewer complications without influencing recurrence. However, if patients cannot undergo surgery immediately, endoscopic retrograde biliary drainage will be applicable to help the preservation of nutritional status, which can have an impact on survival.

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial).

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

Intragastric free cancer cells may be attached to automatic staplers during anastomosis in patients with gastric cancer.

BACKGROUND: Automatic staplers are often used to reconstruct the digestive tract during surgeries for gastric cancer. Intragastric free cancer cells adhering to automatic staplers may come in contact with the laparoscopic port area and progress to port site recurrence. This study aimed to investigate the presence/absence of cancer cells adhering to automatic staplers during gastric cancer surgery using cytological examinations. We further determined the positive predictive clinicopathological factors and clinical implications of free cancer cells attached to automatic staplers. METHODS: This study included 101 patients who underwent distal gastrectomy for gastric cancer. Automatic staplers used for anastomosis in gastric cancer surgeries were shaken in 150 ml of saline solution to collect the attached cells. Papanicolaou stains were performed. We tested the correlation between cancer-cell positivity and clinicopathological factors to identify risk factors arising from the presence of attached cancer cells to the staplers. RESULTS: Based on the cytology, cancer cells were detected in 7 of 101 (6.9%) stapler washing fluid samples. Univariate analysis revealed that circular staplers, type 1 tumors, and positive lymph nodes were significantly associated with higher detection of free cancer cells adhering to staplers. No significant differences in other factors were detected. Of the seven cases with positive cytology, one developed anastomotic recurrence. CONCLUSIONS: Exfoliated cancer cells adhered to the automatic staplers used for anastomoses in 6.9% of the staplers used for distal gastrectomies in patients with gastric cancer. Staplers used for gastric cancer surgeries should be handled carefully.

A multicenter validation study for determining the condition of nonanatomical or minor anatomical hepatectomies satisfying technical difficulty of current high-level hepatectomy certificated by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: The current high-level hepatectomy (HLH) is certified by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), comprising only anatomical hepatectomies above Couinaud's segmentectomy. This multicenter study aimed to identify the conditions of non-HLH that satisfy equivalent technical difficulties to HLH. METHODS: Between 2018 and 2021, 595 first open hepatectomies without biliary reconstruction (374 HLHs and 221 non-HLHs) were performed in the five institutions. Non-HLHs belonging to at least one of the three conditions; depth of hepatectomy ≥5 cm, number of resections ≥3 locations and at least one location with a depth of hepatectomy ≥3 cm, and hepatectomy involving the paracaval portion of the caudate lobe was proposed as the candidate for difficult non-HLH. The technical difficulty was estimated by the operative time and blood loss. RESULTS: Difficult non-HLHs were neither associated with shorter operative time (373 min vs. 354 min, p = .184) nor lesser blood loss than those with HLHs (503 mL vs. 436 mL, p = .126). Postoperative complications such as Clavien-Dindo classification grade III or more were not significant between the two groups (18.6% vs. 13.4%, p = 0212). CONCLUSIONS: Difficult non-HLHs were associated with no lesser technical difficulty than those with HLH.

Physical frailty recovery is slower than mental frailty recovery after non-cardiac surgery in older adult patients.

PURPOSE: Frailty is characterized by fragility and decline in physical, mental, and social activities; it is commonly observed in older adults. No studies have reported frailty status changes between the preoperative and postoperative periods, including mental and cognitive factors. Therefore, this study investigated frailty factors, including mental and cognitive functions, that change after non-cardiac surgery in older adults. METHODS: Patients aged ≥ 75 years who underwent non-cardiac surgery were surveyed using five tools (Eastern Cooperative Oncology Group-Performance Status (PS); handgrip strengths; Japan-Cardiovascular Health Study index (J-CHS index); Mini-Mental State Examination (MMSE); and Geriatric Depression Scale) for comprehensive evaluation of perioperative functions. The results before surgery, at discharge, and during follow-up at the outpatient clinic were compared. RESULTS: Fifty-three patients with a median age of 80 (IQR, 77-84) years were evaluated. MMSE scores did not change during the perioperative period. The PS and J-CHS index worsened significantly at discharge and did not improve at the outpatient clinic follow-up. The dominant handgrip strength decreased after surgery (p < 0.001) but improved during follow-up. Additionally, nondominant handgrip strength decreased after surgery (p < 0.001) but did not recover as much as the dominant handgrip strength during follow-up (p = 0.015). CONCLUSION: Changes in physical frailty and mental and cognitive functions were not identical perioperatively in older adult patients undergoing non-cardiac surgery. Physical frailty did not improve 1 month after surgery, mental function recovered early, and cognitive function did not decline. This study may be important for frailty prevention in older adult patients.

A Prospective Study of Neoadjuvant Gemcitabine Plus Nab-paclitaxel in Patients with Borderline-resectable Pancreatic Cancer.

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

Right hemihepatectomy preserving the fluorescently visible paracaval portion of the caudate lobe.

The paracaval portion (PC) of the caudate lobe is a small area of the liver located in front of the inferior vena cava. Conventional right hemihepatectomy (RH) along the Rex-Cantlie line involves resection of not only the anterior and posterior sections but also the PC behind the middle hepatic vein (MHV). However, to preserve the future liver remnant volume as much as possible, PC-preserving RH may be beneficial in selected patients. We injected an indocyanine green (ICG) solution in the PC portal branch under intraoperative ultrasonography (IOUS) guidance and performed an RH preserving the fluorescently visible PC in a patient with liver metastasis. The patient was a 47-year-old male with a 24 ×10 cm metastatic hepatic tumor from sigmoid colon cancer. CT volumetry revealed that the left hemiliver excluding the caudate lobe was 55%, and the caudate lobe was 5.3%. Before hepatic transection, the ICG solution was injected into the PC portal branch under IOUS guidance. During hepatic transection, the PC was identified as a fluorescent area behind the MHV using a near-infrared imaging system. Thus, the anatomical right-side boundary of the caudate lobe was clearly found. Following RH, the PC was preserved as a fluorescently visible area. The patient had an uneventful recovery. RH preserving the fluorescently visible PC of the liver is a feasible procedure.

Efficacy and safety of regorafenib in combination with immune checkpoint inhibitor therapy as second-line and third-line regimen for patients with advanced hepatocellular carcinoma: a retrospective study.

Background: Despite the emergence of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced hepatocellular carcinoma (HCC), there is an unmet need regarding subsequent treatments in patients that fail ICI. Regorafenib is a vascular endothelial growth factor receptor (VEGFR) inhibitor, which could increase programmed death-ligand 1 (PD-L1) expression in tumors and increase intra-tumoral CD8+ T-cell infiltration by normalizing the cancer vasculature and improving the efficacy of the programmed cell death protein 1 (PD-1) antibody. Thus, we evaluated the combination of regorafenib and a PD-1 inhibitor for advanced HCC patients that had failed combined tyrosine kinase inhibitors (TKIs) plus ICI. Methods: Data of patients with advanced HCC who had failed combined TKIs plus ICI treatment and were afterwards treated with combined regorafenib plus a PD-1 inhibitor were reviewed. All patients had received PD-1 inhibitors as part of the first-line treatment and regorafenib every 4 weeks until disease progression, intolerable toxicities, or physician/patient withdrawal. The clinical data, previous treatment strategies, follow-up imaging results, and adverse events (AEs) during follow-ups were recorded. Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 was used to evaluate AEs and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 was used to evaluate response. The primary endpoint was safety, and the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and duration of response (DOR). Results: From November 15, 2020, to January 31, 2022, data of 17 patients with advanced HCC that met the criteria were reviewed. The cohort included 16 men and 1 woman with a median age of 54 years (interquartile range, 46 to 63 years). Sixteen patients had Child-Pugh class A (n=16, 94.12%) and one with class B (n=1, 15.9%) liver disease. Thirteen patients received second-line treatment, and the remaining patients received third-line treatment. All patients received at least 1 dose of PD-1 inhibitors. The median follow-up duration was 7.62 months. Twelve recipients experienced treatment-related AEs. The most frequent AE (≥5%) included fatigue (17.64%), diarrhea (17.65%), proteinuria (5.88%), bleeding gums (11.76%), and hypertension (11.76%). No grade-4 AE or new safety signals were identified. The ORR and DCR were 41.2% and 64.7%, respectively, and the median PFS was 5.09 months. Conclusions: Regorafenib combined with PD-1 inhibitor is a promising regimen in treating patients with advanced HCC owing to its safety and effectiveness as well as low incidence of serious AEs with its use.

Liver Cancer Study Group of Japan Clinical Practice Guidelines for Intrahepatic Cholangiocarcinoma.

This paper presents the first version of clinical practice guidelines for intrahepatic cholangiocarcinoma (ICC) established by the Liver Cancer Study Group of Japan. These guidelines consist of 1 treatment algorithm, 5 background statements, 16 clinical questions, and 1 clinical topic, including etiology, staging, pathology, diagnosis, and treatments. Globally, a high incidence of ICC has been reported in East and Southeast Asian countries, and the incidence has been gradually increasing in Japan and also in Western countries. Reported risk factors for ICC include cirrhosis, hepatitis B/C, alcohol consumption, diabetes, obesity, smoking, nonalcoholic steatohepatitis, and liver fluke infestation, as well as biliary diseases, such as primary sclerosing cholangitis, hepatolithiasis, congenital cholangiectasis, and Caroli disease. Chemical risk factors include thorium-232, 1,2-dichloropropane, and dichloromethane. CA19-9 and CEA are recommended as tumor markers for early detection and diagnostic of ICC. Abdominal ultrasonography, CT, and MRI are effective imaging modalities for diagnosing ICC. If bile duct invasion is suspected, imaging modalities for examining the bile ducts may be useful. In unresectable cases, tumor biopsy should be considered when deemed necessary for the differential diagnosis and drug therapy selection. The mainstay of treatment for patients with Child-Pugh class A or B liver function is surgical resection and drug therapy. If the patient has no regional lymph node metastasis (LNM) and has a single tumor, resection is the treatment of choice. If both regional LNM and multiple tumors are present, drug therapy is the first treatment of choice. If the patient has either regional LNM or multiple tumors, resection or drug therapy is selected, depending on the extent of metastasis or the number of tumors. If distant metastasis is present, drug therapy is the treatment of choice. Percutaneous ablation therapy may be considered for patients who are ineligible for surgical resection or drug therapy due to decreased hepatic functional reserve or comorbidities. For unresectable ICC without extrahepatic metastasis, stereotactic radiotherapy (tumor size ≤5 cm) or particle radiotherapy (no size restriction) may be considered. ICC is generally not indicated for liver transplantation, and palliative care is recommended for patients with Child-Pugh class C liver function.

Intraoperative Colonoscopy in Laparoscopic Rectal Cancer Surgery Reduces Anastomotic Leakage.

Objectives: Anastomotic leakage (AL) is the most severe complication of colorectal surgery and is a frequent cause of postoperative mortality. This study aimed to identify the risk factors for AL, including the type of air leak test (ALT) performed, in patients undergoing laparoscopic colorectal cancer surgery. Methods: This study involved a retrospective review of 201 patients who underwent elective laparoscopic procedures using circular stapled anastomosis for colorectal cancer between January 2015 and December 2020 at Kyorin University Hospital, Tokyo, Japan. In all cases, the distance from the anal verge to the anastomotic site was within 15 cm. Results: Overall, AL was observed in 16 patients (8.0%). Univariate analysis revealed that the risk factors for AL included diabetes (P = 0.068), tumor location (P = 0.049), level of anastomosis (P = 0.002), number of linear stapler firings (P = 0.007), and intraoperative colonoscopy (IOCS; P = 0.069). Multivariate analysis revealed that the level of anastomosis (P = 0.029) and IOCS (P = 0.039) were significant and independent risk factors for AL. One of the 107 patients undergoing ALT without IOCS and 3 of the 94 patients undergoing ALT with IOCS were proven to be positive for air leak. However, these four patients underwent additional suturing intraoperatively and developed no AL following surgery. Conclusions: This study identified the level of anastomosis and ALT with IOCS as predictors for AL. The results of our study indicate that ALT with IOCS may be more effective than ALT without IOCS in the diagnosis and prevention of AL.

Trends in the surgical treatment for pancreatic cancer in the last 30 years.

Pancreatic cancer has the poorest prognosis among digestive cancers. During the 1990s, the 5-year survival rate of surgical patients with pancreatic cancer was 14% in Japan. However, survival rates have increased to 40% in the 2020s due to the refinement of surgical procedures and the introduction of perioperative chemotherapy. Several pivotal randomized controlled trials have played an indispensable role to establish each standard treatment strategy. Resectability of pancreatic cancer can be classified into resectable, borderline resectable, and unresectable based on the anatomic configuration, and multidisciplinary treatment strategies for each classification have been revised rapidly. Investigation of superior perioperative adjuvant treatments for resectable and borderline resectable pancreatic cancer and the establishment of optimal conversion surgery for unresectable pancreatic cancer are the progressive subjects.