Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

BACKGROUND: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. AIM: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. DISCUSSION: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Impact of Interferon on the Prognosis of Hepatitis C Virus-Related Hepatocellular Carcinoma Patients with a Sustained Virological Response -An Additional Comparison Between Preoperative and Postoperative Sustained Virological Response.

BACKGROUND: Several studies have reported that interferon (IFN) therapy improves the prognosis of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), especially for patients who have achieved a sustained virological response (SVR). We retrospectively evaluated the clinicopathological outcomes of patients who acquired an SVR through IFN therapy pre- or post-hepatectomy for treatment naïve HCC. METHOD: Among the 305 HCV-related HCC patients entered in this study, 59 patients (SVR group) achieved an SVR after IFN therapy and received hepatectomy either after or before achieving an SVR (n=36 and n=23, respectively), while the remaining 179 patients (control group) did not receive IFN therapy, or did not achieve an SVR through IFN therapy (n=67). RESULTS: In the SVR group, the overall survival (OS) and disease-free survival (DFS) rates were significantly higher than in the control group. We evaluated the prognosis of patients with an SVR achieved pre- or post-hepatectomy separately. There were no significant differences in OS and DFS. CONCLUSION: This result suggests that the prognosis of naïve HCC may be improved by additional INF therapy to achieve SVR status after hepatectomy.

Salvage PTBD With Chemotherapy Improves Survival in Patients With Unresectable Malignant Biliary Obstruction - A Single Center Retrospective Study.

BACKGROUND/AIM: Malignant biliary obstruction (MBO) is a life-threatening condition. We aimed to investigate the outcome of salvage percutaneous transhepatic biliary drainage (PTBD) in patients with unresectable MBO due to failure of management by endoscopic retrograde cholangiopancreatography (ERCP) and/or prior surgical bypass. PATIENTS AND METHODS: Fifty-two consecutive patients (mean age, 69 years; 44.2% women) underwent salvage PTBD between 2013 and 2020. RESULTS: The median overall survival rate was 4.2 months, with a 95% confidence interval (CI) of 1.9-5.7. The median overall survival (OS) were 11.1 months and 1.9 months for patients who underwent chemotherapy (n=17) and best supportive care (n=35), respectively (p=0.0005). Independent factors predicting poor outcome were best supportive care, with a hazard ratio (HR) of 3.3 (95%CI=1.3-8.5), American Society of Anesthesiologists physical status classification (ASA) with a HR of 13.5 (95%CI=1.3-136.0) and Eastern Cooperative Oncology Group (ECOG) performance status of 4, with a HR of 3.3 (95%CI=1.0-6.2). CONCLUSION: Salvage PTBD with chemotherapy has the potential to achieve prolonged survival in patients with unresectable MBO, including those with failure of ERCP and/or surgical bypass.

Liberal Application of Portal Vein Embolization for Right Hepatectomy Against Hepatocellular Carcinoma: Strategy to Achieve Zero Mortality for a Damaged Liver.

BACKGROUND/AIM: Right hepatectomy and extended right hepatectomy (Rt-Hr) are identified as risk factors for the development of post-hepatectomy liver failure (PHLF). Although portal vein embolization (PVE) has made it possible to safely perform extended hepatectomy, to ensure safety, in our department, PVE is performed prior to Rt-Hr for hepatocellular carcinoma (HCC) regardless of the resection rate. This study aimed to retrospectively investigate the clinical course of PVE prior to Rt-Hr for HCC cases resected in our department and the appropriateness of our policy by clarifying complications and deaths. PATIENTS AND METHODS: The target period was from 2005 to 2020. Among the HCC cases resected at our hospital, those in which PVE was performed prior to Rt-Hr were included in this study. For PHLF, the definition of the International Study Group of Liver Surgery was used. The Clavien-Dindo classification was used for postoperative complications. Perioperative mortality was defined as the overall mortality within 30 days following surgery and surgery-related deaths within 90 days following surgery. RESULTS: A total of 79 cases were included. Rt-Hr was possible in all cases after PVE and there were no cases in which serious complications occurred after PVE. PHLF was found in 14 cases (17.7%)/5 cases (6.4%)/0 cases (0%) of Grade A/B/C, respectively. Regarding postoperative complications, there were no Grade IV, and Grade IIIa/IIIb were found in 13 cases (16.5%). There were no perioperative deaths. CONCLUSION: Our department's policy of performing PVE prior to all Rt-Hr was considered to be a safe and reasonable treatment strategy.

Hematogenous Dissemination of Tumor Cells in Hepatocellular Carcinoma: Comparing Anterior and Non-anterior Approach Hepatectomy.

BACKGROUND/AIM: Studies have indicated that liver mobilization during hepatectomy could cause the dissemination of tumor cells. However, the data are still limited in terms of the relationship between circulating tumor cells (CTCs) and surgical procedures. PATIENTS AND METHODS: Fifteen patients who underwent hepatectomy for primary hepatocellular carcinoma (HCC) were included in the study. Blood samples were collected from the portal vein, central vein, and peripheral artery at three time points, namely, before mobilization (BM) of the liver, during transection (DT) of parenchyma, and after resection (AR) of the tumor. To detect CTCs, a real-time PCR assay was performed using primers for the epithelial cell adhesion molecule, cytokeratin 18, and glypican 3. Patients were divided into anterior approach (AA) and non-AA (NA) groups. In the AA group, patients underwent an initial hilar vascular dissection followed by a liver hanging maneuver during transection. RESULTS: Seven patients were allocated to the AA group, and eight to the NA group. In the NA group, CTC levels in the portal vein were significantly increased at DT and AR compared to BM. In cases with large HCC (>70 mm), CTC levels in central venous blood were significantly increased at DT and AR in the NA group. CONCLUSION: The AA liver resection technique may minimize CTC dissemination, improving the prognosis of patients with HCC.

Achieving Carnot efficiency in a finite-power Brownian Carnot cycle with arbitrary temperature difference.

Achieving the Carnot efficiency at finite power is a challenging problem in heat engines due to the trade-off relation between efficiency and power that holds for general heat engines. It is pointed out that the Carnot efficiency at finite power may be achievable in the vanishing limit of the relaxation times of a system without breaking the trade-off relation. However, any explicit model of heat engines that realizes this scenario for arbitrary temperature difference has not been proposed. Here, we investigate an underdamped Brownian Carnot cycle where the finite-time adiabatic processes connecting the isothermal processes are tactically adopted. We show that in the vanishing limit of the relaxation times in the above cycle, the compatibility of the Carnot efficiency and finite power is achievable for arbitrary temperature difference. This is theoretically explained based on the trade-off relation derived for our cycle, which is also confirmed by numerical simulations.

Repeated Resection for Recurrent Metastatic Solid Pseudopapillary Neoplasm of the Pancreas.

BACKGROUND Solid pseudopapillary neoplasm (SPN) accounts for 1.0% to 2.0% of all pancreatic neoplasms. SPN generally has good prognosis after surgery; however, 10% to 15% of patients have local recurrence or distant metastasis. There have been a few reports of successful surgical resection of isolated recurrent tumors after radical resection and sporadic reports of multiple metastasectomies. Herein, we present a case of recurrent SPN treated by repeated surgeries. CASE REPORT A 49-year-old woman was referred to our hospital with jaundice and right upper abdominal pain. Computed tomography (CT) scanning revealed a 73×43-mm heterogeneous mass in the pancreatic head. We performed a pancreatoduodenectomy and diagnosed SPN. The patient was discharged without any complications and was followed up by CT once every 6 to 12 months. Six years later, a 15×15-mm tumor was detected in Couinaud segment VI of the liver. A liver biopsy showed a pathological match to the pancreatic tumor. We performed a partial hepatectomy, and the pathology report confirmed metastatic SPN. At 8 and 10 years after the initial surgery, the patient underwent further partial hepatectomies for confirmed solitary liver metastases of SPN. The Ki-67 index increased for each metastasis identified (initial tumor, 1.88%; 6 years, 7.38%; 8 years, 5.53%; 10 years, 11.22%). No further masses were detected, and the patient survived more than 10 years following surgery. CONCLUSIONS Despite histological transformation to high-grade malignant disease, repeated aggressive surgical resection led to long-term survival in our patient with SPN.

Hepatocellular adenoma initially diagnosed as hepatocellular carcinoma with resistance to proton beam radiotherapy - A case report.

INTRODUCTION AND IMPORTANCE: Hepatocellular adenoma (HCA) is a rare liver tumor. We report a case of a radio-resistant liver tumor that was removed surgically and found to be HCA. CASE PRESENTATION: A 37-year-old Japanese man was incidentally diagnosed with a liver tumor. He had no history of viral hepatitis nor metabolic disorders. MRI revealed a tumor enhancing in arterial phase, followed by washout in late phase, and hypointensity in hepatobiliary phase. A diagnosis of hepatocellular carcinoma (HCC) was made and surgery was advised. However, the patient chose proton beam radiotherapy. Although the tumor initially shrunk, it increased in size thereafter. Therefore, anterior sectionectomy was performed. Histology revealed proliferation of hepatocytes without cytologic atypia. On immunohistochemistry, CRP, SAA, GS, L-FABP, and nuclear expression of ß-catenin were positive. A final diagnosis of mixed inflammatory and ß-catenin activated HCA was made. CLINICAL DISCUSSION: HCA is associated with obesity. The present case was a slightly obese man without history of viral hepatitis. In such cases, HCA should be considered. In the present case, proton beam radiotherapy was performed for a diagnosis of HCC. However, the tumor was radio-resistant. CONCLUSION: HCA shows an almost equal male to female ratio in the Asian population. Molecular classification is vital in the management of HCA. HCC and HCA are often difficult to differentiate; tumor biopsy is necessary for patients with atypical imaging findings and in younger patients without underlying liver disease. Since the effectiveness of radiation therapy on HCA has not been reported, surgery should be preferred.

Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel Regimen for Borderline Resectable Pancreatic Cancer with Arterial Involvement: A Prospective Multicenter Single-Arm Phase II Study Protocol.

INTRODUCTION: Although neoadjuvant treatment is recommended for patients with borderline resectable pancreatic cancer (BRPC), no standard neoadjuvant regimen has been established for BRPC with arterial involvement (BRPC-A), which is associated with a higher risk of margin-positive resection and poorer prognosis than BRPC with only venous involvement. Gemcitabine plus nab-paclitaxel (GnP) has been reported to significantly reduce tumor size in metastatic pancreatic cancer, and some retrospective studies suggested that neoadjuvant GnP for BRPC improved resectability and survival. METHODS AND ANALYSIS: A prospective multicenter single-arm phase II study is conducted to evaluate the safety and efficacy of GnP as neoadjuvant chemotherapy for BRPC-A. The primary endpoint is the R0 resection rate. The secondary endpoints are the neoadjuvant chemotherapy response rate, resection rate, pathological response rate, incidence rate of adverse events, and quality of life. ETHICS AND DISSEMINATION: This study protocol was approved by the institutional review board of Kyushu University (no. 181). The results will be published in a peer-reviewed journal and will be presented at medical meetings. HIGHLIGHTS: Strategy for borderline resectable pancreatic cancer involving arteries (BRPC-A).There is no standard regimen for neoadjuvant chemotherapy for BRPC-A.Gemcitabine plus nab-paclitaxel (GnP) shows significant tumor shrinkage.Neoadjuvant GnP for BRPC-A increases resectability and margin-negative resection.

Compatibility of Carnot efficiency with finite power in an underdamped Brownian Carnot cycle in small temperature-difference regime.

We study the possibility of achieving the Carnot efficiency in a finite-power underdamped Brownian Carnot cycle. Recently, it was reported that the Carnot efficiency is achievable in a general class of finite-power Carnot cycles in the vanishing limit of the relaxation times. Thus, it may be interesting to clarify how the efficiency and power depend on the relaxation times by using a specific model. By evaluating the heat-leakage effect intrinsic in the underdamped dynamics with the instantaneous adiabatic processes, we demonstrate that the compatibility of the Carnot efficiency and finite power is achieved in the vanishing limit of the relaxation times in the small temperature-difference regime. Furthermore, we show that this result is consistent with a trade-off relation between power and efficiency by explicitly deriving the relation of our cycle in terms of the relaxation times.

Geriatric nutritional risk index predicts prognosis in hepatocellular carcinoma after hepatectomy: a propensity score matching analysis.

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child-Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p < 0.0001, p < 0.0001, p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598-2.4586; p < 0.0001, and HR, 1.5452; 95% CI 1.0345-2.3079; p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.

Laparoscopic left hepatectomy for a patient with intrahepatic cholangiocarcinoma metastasis in the falciform ligament: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is primary cancer of the liver with poor prognosis because of its high potential for recurrence and metastasis. We experienced a rare case of ICC with hematogenous metastasis to the falciform ligament. We aimed to clarify the route of metastasis to the mesentery by increasing the accuracy of preoperative imaging and establish a hepatectomy to control cancer. CASE PRESENTATION: An 85-year-old woman was referred to our hospital for a detailed study of progressively increasing liver tumors. She had no subjective symptoms. Her medical history showed hypertension, aneurysm clipping for cerebral hemorrhage, and gallstones. A detailed physical examination and laboratory data evaluation included tumor markers but did not demonstrate any abnormalities. On computed tomography scan, contrast-enhanced ultrasound, and magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid, the tumor appeared to be located in liver segment IV, protruding outside the liver. It appeared to contain two distinct components; we suspected ICC in the intrahepatic tumor component. Laparoscopic observation revealed that the extrahepatic lesion was an intra-falciform ligament mass; laparoscopic left hepatectomy was performed. Microscopically, the main tumor in segment IV was 15 mm in diameter and was diagnosed as moderately and poorly differentiated ICC. The tumor of the intra-falciform ligament was not continuous with the main intrahepatic nodule and was also diagnosed as ICC with extensive necrosis. There were no infiltrates in the round ligament of the liver, and several tumor thrombi were found in the small veins of the falciform ligament. CONCLUSIONS: To date, there have been a few reports of metastases of primary liver cancer to the falciform ligament. At the time of preoperative imaging and pathological diagnosis, this case was suggestive of considering that the malignant liver tumor might be suspected of metastasizing to the falciform ligament. Our case improves awareness of this pathology, which can be useful in the future when encountered by hepatic specialists and surgeons.

The Expression of PEDF and its Putative Receptors in Hepatocellular Carcinoma and Background Liver Tissue.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) remains one of the biggest medical issues. Pigment epithelial-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF interacts with its two receptors, adipose triglyceride lipase (ATGL) and laminin receptor (LR). MATERIALS AND METHODS: We conducted immunohistochemical staining for PEDF, LR and ATGL in 151 resected HCCs and their background liver tissues. RESULTS: High expression of LR in HCC was associated with high histological grade and portal vein invasion, while high expression of PEDF in HCC was associated with absence of portal vein invasion. High LR expression in background liver was statistically associated with low serum albumin levels and was an independent prognostic factor of worse outcomes. No cases with more than 5% fatty degeneration in the background liver tissue showed high PEDF expression. CONCLUSION: PEDF/LR/ATGL could be potential biomarkers in HCC and various chronic hepatic disorders.

Successful nonoperative management by endoscopic and percutaneous drainage for penetrating pancreatic duct injury: a case report.

BACKGROUND: Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage. CASE PRESENTATION: A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged. CONCLUSIONS: Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

Laparoscopic Liver Resection Using a Silicone Band Retraction Method (With Video).

BACKGROUND: The success of laparoscopic liver resection (LLR) depends on stable and full exposure of the parenchymal transection plane. We evaluated the efficacy of LLR using a silicone band retraction method for lesions in the anterolateral and posterosuperior segments. METHODS: We retrospectively analyzed 189 consecutive patients who had undergone LLR in our hospital between July 2010 and July 2020. They were divided into 2 groups according to whether LLR was performed before (conventional group; n=64) or after (silicone band group; n=125) the introduction of the silicone band retraction method. RESULTS: The silicone band group demonstrated significantly less blood loss than that by the conventional group. The mean operative time and the hospital stay in the silicone band group were obviously shorter than that in the conventional group. The open conversion rate and the major complication rate were significantly lower in the silicone band group than that in the conventional group. CONCLUSION: The silicone band retraction method is a useful approach that results in a safe LLR.

Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer.

The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non-advanced and 301 advanced-stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide-specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8-2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4-9.9; P<0.01). 'Immune boosting' was defined when IgG levels before vaccination increased more than 2-fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive-response rates and peptide-specific IgG levels in pre- and post-vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre-vaccination factors associated with reduced clinical benefits were high c-reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post-vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre-vaccination inflammatory signatures, rather than pre- or post-vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer.

Central hepatopancreatoduodenectomy-oncological effectiveness and parenchymal sparing option for diffusely spreading bile duct cancer: report of two cases.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) for diffusely spreading bile duct cancer (DSBDC) usually involves a major hepatectomy and a concomitant pancreatoduodenectomy, and is still challenging surgery because of postoperative liver failure. The present case report demonstrated two cases of DSBDC where we could achieve successful HPD with central liver resection (CHPD) as liver parenchymal sparing surgery. CASE PRESENTATION: In Case 1, endoscopic retrograde cholangiography (ERC) with multiple biopsies revealed that she had DSBDC with Bismuth-Corlette type IIIA. 3D integrated images reconstructed by contrast enhanced CT and CT with drip infusion cholecystocholangiography data revealed the right antero-ventral bile duct (RAVD) confluent to the right hepatic duct and the right antero-dorsal bile duct (RADD) independently confluent to the right posterior bile duct (RPD). Tumor extended common bile duct including intrapancreatic bile duct to the left hepatic duct and RAVD, but the RADD and RPD were spared. Because the future liver remnant (FLR) was assumed not to achieve desirable volume by preoperative portal vein embolization for left or right trisegmentectomy, CHPD including resection of the segments IV and I, and the right antero-ventral segment was done and achieved R0. This procedure is tailored to the anatomical extent of disease in the context of variable biliary anatomy as a modified CHPD, and to our knowledge, this is the first reported case of modified CHPD with antero-dorsal segment preservation. In Case 2, preoperative imaging revealed DSBDC with Bismuth Corlette type IIIA. FLR volume was assumed insufficient for major hepatectomy, CHPD including resection of the segments IV and I, and the right anterior sector was done with R0. The remnant liver volumes of these cases were spared by 55.1% and 25% respectively, and postoperative course was uneventful in both. CONCLUSION: CHPD should be considered a valid option for well-selected cases of DSBDC. This is the first case report of modified CHPD with antero-dorsal segment preservation.

Spontaneous regression of lung metastases in hepatocellular carcinoma: A case report.

INTRODUCTION: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare condition. However, although there have been multiple reports of spontaneous regression, the definitive pathogenic mechanism of this phenomenon is still unclear. CASE PRESENTATION: We encountered a case of a 78-year-old man who was undergoing dialysis for end-stage kidney disease with hepatitis C virus-associated chronic hepatitis presenting with HCC. The patient had previously undergone right lobectomy of the liver, but the cancer recurred with multiple lung metastases after 5 months. Approximately 13 months after the initial diagnosis of recurrence, the lung metastases decreased in size and eventually resolved without any anticancer therapy. The patient remains alive for over 41 months after recurrence. DISCUSSION: Based on our case and literature, Hypoxia with hypotension due to hemodialysis can reduce the blood and oxygen supply of the body, which may lead to the spontaneous regression of the metastatic tumors. CONCLUSION: We herein reported a case of spontaneous regression of HCC undergoing dialysis.