Development of a transformer model for predicting the prognosis of patients with hepatocellular carcinoma after radiofrequency ablation.

INTRODUCTION: Radiofrequency ablation (RFA) is a widely accepted, minimally invasive treatment modality for patients with hepatocellular carcinoma (HCC). Accurate prognosis prediction is important to identify patients at high risk for cancer progression/recurrence after RFA. Recently, state-of-the-art transformer models showing improved performance over existing deep learning-based models have been developed in several fields. This study was aimed at developing and validating a transformer model to predict the overall survival in HCC patients with treated by RFA. METHODS: We enrolled a total of 1778 treatment-naïve HCC patients treated by RFA as the first-line treatment. We developed a transformer-based machine learning model to predict the overall survival in the HCC patients treated by RFA and compared its predictive performance with that of a deep learning-based model. Model performance was evaluated by determining the Harrel's c-index and validated externally by the split-sample method. RESULTS: The Harrel's c-index of the transformer-based model was 0.69, indicating its better discrimination performance than that of the deep learning model (Harrel's c-index, 0.60) in the external validation cohort. The transformer model showed a high discriminative ability for stratifying the external validation cohort into two or three different risk groups (p < 0.001 for both risk groupings). The model also enabled output of a personalized cumulative recurrence prediction curve for each patient. CONCLUSIONS: We developed a novel transformer model for personalized prediction of the overall survival in HCC patients after RFA treatment. The current model may offer a personalized survival prediction schema for patients with HCC undergoing RFA treatment.

Clinical utility of postablation liver tumor biopsy and possibility of gene mutation analysis.

AIM: Radiofrequency ablation (RFA) is regarded as a first-line treatment for hepatocellular carcinoma (HCC) at an early stage. When treated with RFA, tumor biopsy may not be performed due to the risk of neoplastic seeding. We previously revealed that the risk of neoplastic seeding is significantly reduced by performing biopsies after RFA. In this study, we investigated the possibility of pathological evaluation and gene mutation analysis of post-RFA tumor specimens. METHODS: Radiofrequency ablation was undertaken on diethylnitrosamine-induced mouse liver tumor, and tumor samples with or without RFA were subjected to whole exome sequencing. Post-RFA human liver tumor specimens were used for detection of TERT promoter mutations and pathological assessment. RESULTS: The average somatic mutation rate, sites of mutation, and small indels and base transition patterns were comparable between the nontreated and post-RFA tumors. We identified 684 sites of nonsynonymous somatic substitutions in the nontreated tumor and 704 sites of nonsynonymous somatic substitutions in the post-RFA tumor, with approximately 85% in common. In the human post-RFA samples, the TERT promoter mutations were successfully detected in 40% of the cases. Pathological evaluation was possible with post-RFA specimens, and in one case, the diagnosis of adenocarcinoma was made. CONCLUSION: Our findings suggest that post-RFA liver tumor biopsy is a useful and safe method for obtaining tumor samples that can be used for gene mutation analysis and for pathological assessment.

Steroid administration for ischemic complications after radiofrequency ablation: A retrospective study.

AIM: The aim of this study was to evaluate the effects of steroids on ischemic complications after radiofrequency ablation. METHODS: A total of 58 patients with ischemic complications were divided into two groups according to corticosteroid use or non-use. RESULTS: A total of 13 patients who were administered steroids had a shorter duration of fever than those who were not administered steroids (median 6.0 vs. 2.0 days; p < 0.001). Linear regression analysis showed that steroid administration was associated with a reduction of 3.9 days in the duration of fever (p = 0.008). CONCLUSIONS: Steroid administration for ischemic complications after radiofrequency ablation may reduce the risk of fatal outcomes by blocking systemic inflammatory reactions.

Improved prognosis of hepatitis C-related hepatocellular carcinoma in the era of direct-acting antivirals.

The prognostic impact of direct-acting antivirals (DAAs) on patients with hepatitis C-related hepatocellular carcinoma (C-HCC) is still unclear. This study aimed to evaluate the prognosis of C-HCC in the DAA era. We enrolled 1237 consecutive patients with treatment-naive C-HCC who underwent radical radiofrequency ablation between 1999 and 2019. We also enrolled 350 patients with nonviral HCC as controls. We divided these patients into three groups according to the year of initial treatment: 1999-2005 (cohort 1), 2006-2013 (cohort 2), and 2014-2019 (cohort 3). The use of antiviral agents and their effect in patients with C-HCC was investigated. Overall survival was evaluated for each cohort using the Kaplan-Meier method and a multivariable Cox proportional hazards regression model. Sustained virologic response (SVR) was achieved in 52 (10%), 157 (26%), and 102 (74%) patients with C-HCC in cohorts 1-3, respectively. The 3- and 5-year survival rates of patients with C-HCC were 82% and 59% in cohort 1; 80% and 64% in cohort 2; and 86% and 78% in cohort 3, respectively (p = 0.003). Multivariable analysis adjusted for age, liver function, and tumor extension showed that the prognosis of C-HCC improved in cohort 3 compared to cohort 1 (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], 0.32-0.73; p < 0.001), whereas the prognosis of nonviral HCC did not improve significantly (aHR, 0.96; 95% CI, 0.59-1.57; p = 0.88). The prognosis of C-HCC drastically improved with the advent of DAAs.

[A case of granulocyte-colony stimulating factor-producing gallbladder adenosquamous carcinoma with rapidly-growing recurrence of liver metastasis in early postoperative period].

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.

A patient with cystic duct remnant calculus treated by laparoscopic surgery combined with near-infrared fluorescence cholangiography.

BACKGROUND: The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury. CASE PRESENTATION: The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain. CONCLUSION: Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy.

Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume.

BACKGROUND: Serum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR. METHODS: Patients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated. RESULTS: Of 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018). CONCLUSIONS: Improved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.

[A Case of Primary Anal Fistula Cancer with Extensive Intrapelvic Spreading That Was Successfully Treated with Bevacizumab plus mFOLFOX6].

The patient was a 68-year-old man who had an anal fistula for>10 years. He was referred to our institution after visiting a local physician with left femoral pain as the main complaint and received a diagnosis of high inflammatory response. We then found discharge of pus in the perianal region during a medical examination. We also found an extensive intrapelvic tumor during a computed tomography(CT)/magnetic resonance imaging examination. In addition, the level ofa tumor marker and inflammatory response were high. To control the inflammation, we performed seton drainage and sigmoid colostomy. On the basis of the pathological findings from the mucus component, we confirmed a diagnosis of fistula cancer. Considering that the progressive lesion had extensively spread, we decided to initiate chemotherapy alone because ofthe absence ofan indication for radiotherapy. We administered bevacizumab plus mFOLFOX6, and partial response was observed on a CT scan. We could control the progression ofthe disease for>6 months. The present case suggests that bevacizumab plus mFOLFOX6 can be an effective regimen for unresectable advanced fistula cancers.

Validation of the 2012 Fukuoka Consensus Guideline for Intraductal Papillary Mucinous Neoplasm of the Pancreas From a Single Institution Experience.

OBJECTIVES: The 2012 Fukuoka consensus guideline has stratified the risks of malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into "high-risk stigmata" (HRS) and "worrisome feature" (WF). This study aimed to evaluate its clinical validity based on a single institution experience. METHODS: Eighty-nine patients who underwent surgical resection with pathological diagnosis of IPMN were retrospectively studied. RESULTS: High-risk stigmata was significantly correlated with the prevalence of malignant IPMN as compared with WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis indicated that all the factors in HRS and WF had statistical significance. Whereas multivariate analysis revealed only enhanced solid component (odds ratio [OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS and WF by different numbers of positive factors resulted in improved predictive value. The area under the curve of HRS score was significantly lower than that of WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001). CONCLUSIONS: As supplementary to the 2012 Fukuoka guideline, we suggest that calculating scores of WF and HRS may have superior diagnostic accuracy in predicting malignant IPMN.

Pancreatic volume is one of the independent prognostic factors for resectable pancreatic ductal adenocarcinomas.

BACKGROUND: It is well known that pancreatic ductal adenocarcinoma (PDAC) is accompanied with pancreatic atrophy and fibrosis. We previously reported the correlation between pancreatic volume and body surface area (BSA) and significant reduction of BSA-adjusted pancreatic volume in pancreatic cancer patients. We evaluated potential correlation between BSA-adjusted pancreatic volume and PDAC prognosis. METHODS: The study subjects were 48 pancreatic cancer patients received pancreatectomy at our department from June 2006 to September 2012. Pancreatic volumetry was retrospectively performed using the images obtained from multidetector computed tomography before the surgery. BSA-adjusted pancreatic volumes were calculated and analyzed for potential correlation with the prognosis. RESULTS: Average BSA-adjusted pancreatic volume among 48 cases was 35.4 ± 11.9 ml/m(2) . Types of surgery included 24 cases with pancreaticoduodenectomy and 24 cases with distal pancreatectomy. The cases with BSA-adjusted pancreatic volume less than 40 ml/m(2) had significantly poorer prognosis compared to the cases of 40 ml/m(2) and greater (3-year survival rate: 32.4% vs. 64.3%). Statistical analysis identified four prognosis factors, i.e. BSA-adjusted pancreatic volume less than 40 ml/m(2) , postoperative adjuvant chemotherapy, lymph node metastasis and lymphatic invasion. CONCLUSIONS: This study demonstrated BSA-adjusted pancreatic volume as a prognosis factor for PDAC and the volume of 40 ml/m(2) is considered to be the cutoff value.

[Advanced gastric cancer showing complete response to neoadjuvant chemotherapy with CPT-11 and S-1-a case report].

We report a case of advanced gastric cancer that showed a complete histological response to neoadjuvant chemotherapy. The patient, a 56-year-old man, was diagnosed as having advanced gastric cancer with lymph node metastases( cT3 cN1 cH0 cP0 cM0, cStageIIIA). He was initially treated with combined neoadjuvant chemotherapy comprising CPT-11+S-1. S-1(120 mg/day)was administered orally for 21 days, followed by CPT-11(130 mg/body)divon days 1 and 15. The primary lesion and lymph node metastases were diminished by 2 courses of chemotherapy, and no serious toxicities were observed. Distal gastrectomy and lymph node dissection(D2)were performed. Only a small ulcer was observed on the resected stomach. Histological examination of the resected stomach and lymph nodes revealed no remaining viable cancer cells. The patient has been doing well without any recurrence for 1 year since the start of treatment.