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.

Refractory postoperative pancreatic fistula following laparoscopic distal pancreatectomy for pancreatic cancer caused by incomplete pancreas divisum: a case report.

Pancreas divisum (PD) represents a prevalent congenital pancreatic variant, typically arising from the failure of fusion between the ventral and dorsal pancreatic ducts. This condition is frequently associated with recurrent pancreatitis. We herein present a case involving an incomplete PD diagnosis following the identification of a refractory postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (DP) for pancreatic cancer. A 74-year-old female patient, who had undergone laparoscopic DP for pancreatic cancer, developed a POPF accompanied by intraabdominal bleeding, necessitating urgent intervention radiology to avert life-threatening complications. Following this, intraabdominal drainage was performed through an intraoperative drainage root. Subsequent fistulography and endoscopic retrograde pancreatography unveiled the presence of an incomplete PD for the first time. Consequently, a stent was placed in the Santorini duct. However, the volume of pancreatic juice from the intraabdominal drainage tube exhibited no reduction. Despite repeated attempts to access the pancreatic duct via a guidewire through the drainage tube, these endeavors proved futile. Paradoxically, the removal of the external drainage tube led to a recurrence of intraabdominal abscess formation. Consequently, reinsertion of the drainage tube became imperative. Consideration was given to draining the abscess under endoscopic ultrasonography and performing pancreatic duct drainage. However, due to the diminution of the abscess cavity through the external fistula drainage procedure, coupled with the absence of pancreatic duct dilation and its tortuous course, it was deemed a formidable challenge. the patient necessitated a lifestyle adaptation with a permanently placed percutaneous drainage tube.

Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

Metastatic small cell bladder cancer treated with sequential systemic therapy including pembrolizumab and amrubicin: A case report.

Introduction: Small cell bladder cancer is a relatively rare tumor, representing <1% of all bladder tumors. Amrubicin monotherapy is used as second-line treatment for small cell lung cancer in Japan. Case presentation: A 79-year-old woman presented with gross hematuria and was diagnosed with small cell bladder cancer (T2 or higher). Neoadjuvant chemotherapy with etoposide and cisplatin resulted in a partial response. Robot-assisted radical cystectomy was performed, and radical resection was achieved. As we identified metastasis in the pleura 1 year later, we administered carboplatin and etoposide, which resulted in a partial response. Although pembrolizumab was initiated as maintenance therapy, it was not effective. Amrubicin was given as third-line therapy, and stable disease was achieved without serious adverse effect for 6 months. Conclusion: Although there is no established treatment for metastatic small cell bladder cancer, the current case report suggests the effectiveness of amrubicin in this setting.

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.

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.

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.

Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls.

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red-purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.

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.

The Efficacy and Safety of Nivolumab Plus mFOLFOX6 in Gastric Cancer with Severe Peritoneal Metastasis.

(1) Background: Nivolumab plus chemotherapy is established as a first-line treatment for advanced gastric cancer (AGC). While mFOLFOX6 is commonly used for AGC with severe peritoneal metastasis, the efficacy of nivolumab combined with it remains uncertain. We evaluated the outcomes of nivolumab plus mFOLFOX6 for AGC with severe peritoneal metastasis in clinical practice. (2) Methods: This multicenter retrospective study was conducted between December 2021 and June 2023. We investigated AGC patients with massive ascites or inadequate oral intake due to severe peritoneal metastasis and who received nivolumab plus mFOLFOX6. (3) Results: Among 106 patients treated with nivolumab plus chemotherapy, 21 (19.8%) had severe peritoneal metastasis, with 14 receiving nivolumab plus mFOLFOX6. The median progression-free survival was 7.4 months (95%CI 1.9-10.1), and the median overall survival was 10.7 months (95%CI 5.3-NA), with four patients (28.5%) surviving more than 12 months. Improved ascites and oral intake were observed in 6/14 patients (42.8%) and 10/11 patients (90.9%), respectively. The major grade 3 or more adverse events included leukopenia (28.5%) and neutropenia (21.4%), with no severe immune-related adverse events reported. (4) Conclusions: The safety and moderate efficacy of nivolumab plus mFOLFOX6 were suggested even in AGC patients with severe peritoneal metastasis.

Ultrasonographic findings in nevus lipomatosus cutaneous superficialis: What differentiates this tumor from other soft tissue tumors?

Nevus lipomatosus cutaneous superficialis is a rare, benign hamartoma characterized by mature adipocyte proliferation in the dermis. It is frequently difficult to distinguish clinically from soft tissue tumors, including lipoma, neurofibroma, venous malformation, and angiolipoma. Notably, the classical form, which shows multiple and sometimes enlarged nodules, is difficult to differentiate from liposarcoma based on clinical examination, computed tomography, and magnetic resonance imaging findings. Therefore, to ascertain the utility of ultrasonography in diagnosing nevus lipomatosus cutaneous superficialis, sonographic examinations were performed on eight patients with nevus lipomatosus cutaneous superficialis. All patients had ill-defined hyperechoic masses in the dermis or from the dermis to the subcutis, and the posterior echoes were attenuated in seven patients. Color Doppler sonography revealed no blood flow to the lesions. Ultrasound images were created using the reflections of ultrasound waves at interfaces with different acoustic impedances. Therefore, it is assumed that, in nevus lipomatosus cutaneous superficialis, the ultrasound beam is scattered by ectopic mature adipocytes intermingled with collagen bundles, which are shown as hyperechoic masses. Furthermore, the scattering of the ultrasound beam is thought to reduce tissue penetration, which may attenuate the posterior echo.

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.

The efficacy of STRATAFIX® spiral PDS for vesicourethral anastomosis during robot-assisted laparoscopic radical prostatectomy: a single-center retrospective study.

PURPOSE: To investigate the efficacy of continuous suturing using barbed suture for vesicourethral anastomosis (VUA) during robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS: Seventy-three consecutive patients who underwent RARP by a single surgeon between 2020 and 2022 were retrospectively divided based on the suture type used for VUA: group A, 3-0 poliglecaprone-25 RB-1 needle (Monocryl®), n = 46; group B, 3-0 spiral polydioxanone (PDS) barbed suture with RB-1 needle (STRATAFIX®), n = 27. RESULTS: There was no significant difference in patient background characteristics between groups, including age, body mass index, and clinical stage. However, group B had a significantly shorter operative time, console time, hospital stay, and duration of urethral catheterization. The VUA time was significantly shorter in group B than in group A (17.9 min vs. 10.6 min; p < 0.001). Only 1 case of minor leakage was observed during the intraoperative leak test (1 patient in group A). There was no significant difference in the number of pads used at 1, 3, 6 months and 1 year postoperatively. There were no urethral strictures, and there was no significant difference in pathologic results or postoperative prostate-specific antigen progression between groups. CONCLUSIONS: Our study suggests that the use of barbed suture during VUA for RARP is associated with reduced VUA time.

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.

Bladder stone formation around polyethylene glycol after use of SpaceOAR Hydrogel.

Introduction: Radiation therapy is used as primary, adjuvant, and salvage therapy for prostate cancer. When using radiation therapy, the SpaceOAR® system is considered easy to use and useful for reducing the irradiated dose and toxicity to the rectum. Although SpaceOAR® system have been reported some adverse event including death. Case presentation: A 74-year-old male was diagnosed with prostate cancer of clinical stage cT2aN0M0 and intermediate risk by the National Comprehensive Cancer Network guidelines. We inserted the SpaceOAR® Hydrogel before performing intensity-modulated radiation therapy, as the patient had ulcerative colitis. We did not recognize any complications during or after the procedure, although magnetic resonance imaging revealed hydrogel in the bladder retrospectively. Fourteen months after the procedure, the patient was presented with macrohematuria and we found a bladder stone including hydrogel. Conclusion: We report the first case of a bladder stone after use of SpaceOAR® Hydrogel. We must be careful of taking place it.

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/

Prevalence of psychological distress and associated factors among patients undergoing comprehensive genomic profiling testing: protocol for a multicentre, prospective, observational study.

INTRODUCTION: Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan's health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients' mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan. METHODS AND ANALYSIS: This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2-3 months after T1) and 4-5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists' communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations. TRIAL STATUS: The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026. TRIAL REGISTRATION NUMBER: UMIN000049964.

Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer.

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells. Methods: Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared. Results: Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32-0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00-2.87) and systemic progression (HR, 3.09, 95%CI, 1.95-4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04-8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different. Conclusion: The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.

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.