Publications by authors named "Manabu Morimoto"

Cabozantinib is a multi-kinase inhibitor targeting multiple tyrosine kinases. It improves overall survival and progression-free survival in patients previously treated with sorafenib for advanced hepatocellular carcinoma (HCC) compared to the placebo in the phase 3 CELESTIAL trial. A 71-year-old man presented to our hospital for treatment of HCC with chronic hepatitis C.

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Article Synopsis
  • The study aimed to find important biomarkers for predicting how patients with unresectable hepatocellular carcinoma (u-HCC) respond to a combination treatment of atezolizumab and bevacizumab (ATZ + BV).
  • Researchers evaluated circulating tumor DNA (ctDNA) and levels of various immune-related cytokines in blood samples from 158 u-HCC patients to identify potential indicators of treatment outcomes.
  • Key findings showed that while ctDNA mutations weren't correlated with treatment response, high levels of CXCL9 and low levels of LAG-3 were significant predictors of better progression-free survival and overall survival in patients undergoing ATZ + BV therapy.
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Aim: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients.

Methods: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib.

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Introduction: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC.

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Background: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished.

Methods: We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression.

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Background: The global phase 3 NAPOLI -1 trial of patients with pancreatic ductal adenocarcinoma (PDAC) demonstrated an overall survival (OS) benefit from using liposomal irinotecan and 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) after treatment with gemcitabine (GEM) compared to 5-FU/LV alone. However, the efficacy and safety of this regimen in older patients are not well studied.

Methods: We conducted a single-center retrospective study to compare the therapeutic efficacy of nal-IRI + 5-FU/LV between older and younger patients with cutoff ages of 70 and 75 years, respectively.

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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and surgical resection is the only potentially curative approach. However, the rate of recurrence remains high, particularly within the first 6 months, and is associated with a poor prognosis. The present study evaluated the clinical characteristics and risk factors for early recurrence in pancreatic ductal adenocarcinoma (PDAC) patients who underwent curative resection, regardless of the use of neoadjuvant chemotherapy, to identify predictive factors associated with early recurrence and poor outcomes as well as to determine the optimal treatment strategy for patients at high risk of early recurrence after surgical resection.

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Objective: To investigate the association between body composition and prognosis in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Methods: This cohort study analysed 119 patients who received atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. We investigated the association between body composition and progression-free survival and overall survival.

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Background And Objective: For patients with advanced hepatocellular carcinoma (HCC), the standard of care for many years has been sorafenib. Preliminary data have suggested that the combination of the NAD(P)H:quinone oxidoreductase 1 bioactivatable agent napabucasin plus sorafenib may improve clinical outcomes in patients with HCC. In this phase I, multicenter, uncontrolled, open-label study, we evaluated napabucasin (480 mg/day) plus sorafenib (800 mg/day) in Japanese patients with unresectable HCC.

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Article Synopsis
  • Immune checkpoint inhibitors (ICIs) show promise for advanced hepatocellular carcinoma (HCC), but their link to immune-related adverse events (irAEs) and patient survival is not well-studied.
  • This study analyzed 150 advanced HCC patients who received atezolizumab plus bevacizumab, comparing those who experienced irAEs to those who did not.
  • Results indicated that patients with grade 1/2 irAEs had significantly better progression-free survival (273 days vs. 189 days) and overall survival compared to those without irAEs, indicating that these adverse events may correlate with improved survival outcomes.
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Background: Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma.

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Article Synopsis
  • Cabozantinib demonstrated a favorable risk-benefit ratio for Japanese patients with advanced liver cancer (HCC) based on a phase II study that analyzed data before the final database lock.* -
  • Patients who had previously been treated with sorafenib experienced a median progression-free survival (PFS) of 7.4 months, while those who were naïve to sorafenib had a lower PFS of 3.6 months, with high disease control rates in both groups.* -
  • Overall, cabozantinib showed efficacy with a manageable safety profile, with the most common side effects being skin reactions, diarrhea, and appetite loss, while liver function remained stable for ongoing patients.*
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Sarcopenia often affects patients with various types of cancer, and has been reported to affect patient prognosis and therapeutic effects. However, to the best of our knowledge, there are no reports on the relationship between gemcitabine plus nab-paclitaxel combination therapy (GnP) and sarcopenia in patients with unresectable pancreatic cancer. The present study analyzed the relationship between overall survival (OS), progression-free survival (PFS), response rate, disease control rate, adverse events (AEs) and sarcopenia in patients with pancreatic cancer treated with GnP.

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Background: The preferred regimen for unresectable pancreatic cancer following gemcitabine-based chemotherapy is not well-established. This study compared the efficacy of (ⅰ) liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) versus modified FOLFIRINOX (mFFX) and (ⅱ) nal-IRI/5-FU/LV versus FOLFIRI, respectively, and the safety of the three regimens each other, as second-line chemotherapies for unresectable pancreatic cancer.

Methods: This was a retrospective single-center analysis of all patients who were administered nal-IRI/5-FU/LV, mFFX, or FOLFIRI from December 2014 to July 2021 as second-line chemotherapy for pancreatic cancer.

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Article Synopsis
  • The study evaluates how computed tomography (CT) attenuation values (CTav) can predict tumor necrosis in patients with hepatocellular carcinoma (HCC) who have achieved a complete response (CR) after treatment with lenvatinib.
  • Researchers compared arterial phase CT images with histopathological findings from surgery, determining CTav thresholds indicative of necrosis and confirming the accuracy of these thresholds in a larger patient group.
  • Results indicated that a CTav cut-off of 30.2 HU and a N30-CTav occupancy rate of over 30.6% can effectively identify necrotic tissue and predict lower local recurrence rates after achieving CR in HCC patients.
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Mucinous cystadenocarcinoma (MCAC) with malignant ascites is rare. We report a case of a 28-year-old woman who presented with epigastric pain. The ascites in the Douglas fossa was identified at a nearby gynecology clinic.

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Background: Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial.

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Objective: The aim of the study was to clarify the association of skeletal muscle mass and the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine plus nab-paclitaxel (GnP).

Methods: We included 124 unresectable PDAC patients who received GnP chemotherapy. Skeletal muscle mass of the third lumbar vertebrae (L3) level was measured by computed tomography immediately before GnP initiation, and the skeletal muscle index (L3-SMI) was calculated.

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Introduction: Postoperative pancreatic fistula (POPF) is one of the major critical complications after pancreatic resection. Recently, postoperative acute pancreatitis (POAP), a new concept for a pancreatic-specific complication following pancreatic resection, has been advocated, and its association with POPF has been reported. The present study examined the clinical features of POAP and identified the associations of POAP with POPF and other postoperative morbidities in pancreatic ductal adenocarcinoma (PDAC) patients undergoing pancreatic resection.

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Background: In this study, we investigated the impact of simple measurement of psoas muscle index (PMI) on the tolerability of sorafenib treatment of switch from sorafenib to regorafenib.

Method: This retrospective study enrolled 109 patients with Child-Pugh A hepatocellular carcinoma (HCC) treated with sorafenib. Pretreatment PMI was calculated by measuring and multiplying the greatest anterior/posterior and transverse diameters of the psoas muscles on axial computed tomography images at the L3 vertebral level, and normalizing the sum of bilateral psoas muscle areas by the square of the height in meters.

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Aims: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era.

Methods And Results: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers.

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Background: Although second-line treatment for pancreatic cancer has been proven to have survival benefit, it is not clear which is the most preferred regimen. This study compared the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) and sequential chemotherapy (FOLFIRI/FOLFOX) as a second-line treatment regimen for unresectable pancreatic cancer.

Method: This was a retrospective single-center analysis of all patients who initiated treatment with mFOLFIRINOX or sequential chemotherapy from December 2014 to May 2019 as a second-line treatment for unresectable pancreatic cancer.

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Purpose: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC).

Method: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48).

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Background: Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed.

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Pancreatic cancer frequently involves cancer-associated thromboembolism, which is strongly associated with poor prognosis. Tissue factor, a blood coagulation factor largely produced in cancer patients as a component of extracellular vesicles, plays a key role in the incidence of cancer-associated thromboembolism in patients with pancreatic cancer. However, no prospective studies have been published on the relationship between tissue factor and cancer-associated thromboembolism or patient clinical characteristics, including recent chemotherapy regimens.

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