Clonal analysis of metachronous double biliary tract cancers.

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and ß-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Negative prognostic impact of sarcopenia before and after neoadjuvant chemotherapy for pancreatic cancer.

OBJECTIVES: To elucidate the prognostic impact of sarcopenia before and after neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). METHODS: We retrospectively studied 75 consecutive PC patients who underwent neoadjuvant gemcitabine plus S-1 combination therapy followed by pancreatectomy between 2008 and 2016. According to the skeletal muscle volume index (SMI), the patients were divided into the muscle attenuation group (MAG) and normal group (NG) before or after NAC. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards models. RESULTS: The MAG showed significantly poorer OS than the NG before and after NAC. Pre-NAC, median OS was 20.0 months in the MAG versus 49.0 months in the NG (p = 0.006). Post-NAC, median OS was 21.3 months in the MAG versus 48.8 months in the NG (p = 0.014). Multivariate analysis, excluding muscle attenuation after NAC because of confounding factors and lower hazard ratio (2.08, 95% confidence interval: 1.14-3.78, p = 0.016) than that before NAC (2.14, 1.23-3.70, p = 0.007) by univariate analysis, revealed the following independent prognostic factors: muscle attenuation pre-NAC (2.25, 1.26-4.05, p = 0.007); borderline resectability (1.96, 1.04-3.69, p = 0.038); operative blood loss (2.60, 1.38-4.88, p = 0.003); and distant metastasis (3.31, 1.40-7.82, p = 0.006). CONCLUSIONS: Sarcopenia before and after NAC for PC is suggested to be a poor prognostic factor, with a stronger impact before than after NAC.

Deep learning image reconstruction to improve accuracy of iodine quantification and image quality in dual-energy CT of the abdomen: a phantom and clinical study.

OBJECTIVES: To investigate the effect of deep learning image reconstruction (DLIR) on the accuracy of iodine quantification and image quality of dual-energy CT (DECT) compared to that of other reconstruction algorithms in a phantom experiment and an abdominal clinical study. METHODS: An elliptical phantom with five different iodine concentrations (1-12 mgI/mL) was imaged five times with fast-kilovoltage-switching DECT for three target volume CT dose indexes. All images were reconstructed using filtered back-projection, iterative reconstruction (two levels), and DLIR algorithms. Measured and nominal iodine concentrations were compared among the algorithms. Contrast-enhanced CT of the abdomen with the same scanner was acquired in clinical patients. In arterial and portal venous phase images, iodine concentration, image noise, and coefficients of variation for four locations were retrospectively compared among the algorithms. One-way repeated-measures analyses of variance were used to evaluate differences in the iodine concentrations, standard deviations, coefficients of variation, and percentages of error among the algorithms. RESULTS: In the phantom study, the measured iodine concentrations were equivalent among the algorithms: within ± 8% of the nominal values, with root-mean-square deviations of 0.08-0.36 mgI/mL, regardless of radiation dose. In the clinical study (50 patients; 35 men; mean age, 68 ± 11 years), iodine concentrations were equivalent among the algorithms for each location (all p > .99). Image noise and coefficients of variation were lower with DLIR than with the other algorithms (all p < .01). CONCLUSIONS: The DLIR algorithm reduced image noise and variability of iodine concentration values compared with other reconstruction algorithms in the fast-kilovoltage-switching dual-energy CT. KEY POINTS: • In the phantom study, standard deviations and coefficients of variation in iodine quantification were lower on images with the deep learning image reconstruction algorithm than on those with other algorithms. • In the clinical study, iodine concentrations of measurement location in the upper abdomen were consistent across four reconstruction algorithms, while image noise and variability of iodine concentrations were lower on images with the deep learning image reconstruction algorithm.

Utility of Thin-slice Fat-suppressed Single-shot T2-weighted MR Imaging with Deep Learning Image Reconstruction as a Protocol for Evaluating the Pancreas.

PURPOSE: To compare the utility of thin-slice fat-suppressed single-shot T2-weighted imaging (T2WI) with deep learning image reconstruction (DLIR) and conventional fast spin-echo T2WI with DLIR for evaluating pancreatic protocol. METHODS: This retrospective study included 42 patients (mean age, 70.2 years) with pancreatic cancer who underwent gadoxetic acid-enhanced MRI. Three fat-suppressed T2WI, including conventional fast-spin echo with 6 mm thickness (FSE 6 mm), single-shot fast-spin echo with 6 mm and 3 mm thickness (SSFSE 6 mm and SSFSE 3 mm), were acquired for each patient. For quantitative analysis, the SNRs of the upper abdominal organs were calculated between images with and without DLIR. The pancreas-to-lesion contrast on DLIR images was also calculated. For qualitative analysis, two abdominal radiologists independently scored the image quality on a 5-point scale in the FSE 6 mm, SSFSE 6 mm, and SSFSE 3 mm with DLIR. RESULTS: The SNRs significantly improved among the three T2-weighted images with DLIR compared to those without DLIR in all patients (P < 0.001). The pancreas-to-lesion contrast of SSFSE 3 mm was higher than those of the FSE 6 mm (P < 0.001) and tended to be higher than SSFSE 6 mm (P = 0.07). SSFSE 3 mm had the highest image qualities regarding pancreas edge sharpness, pancreatic duct clarity, and overall image quality, followed by SSFSE 6 mm and FSE 6 mm (P < 0.0001). CONCLUSION: SSFSE 3 mm with DLIR demonstrated significant improvements in SNRs of the pancreas, pancreas-to-lesion contrast, and image quality more efficiently than did SSFSE 6 mm and FSE 6 mm. Thin-slice fat-suppressed single-shot T2WI with DLIR can be easily implemented for pancreatic MR protocol.

Preoperative chemotherapy with Gemcitabine for pancreatic cancer causes zinc deficiency.

OBJECTIVES: The aim of this study was to investigate how preoperative chemotherapy affected the serum zinc concentrations in patients with pancreatic cancer (PC). METHODS: Two hundreds and thirty-one patients with PC who underwent pancreatectomy at our department from 2013 to 2019 were enrolled in this study and measured for the serum zinc concentrations before pancreatectomy. Patient characteristics, course of treatment, and laboratory data were analyzed. RESULTS: One hundred thirty-five patients underwent upfront pancreatectomy and 58 received preoperative Gemcitabine + S1 (GEM + S1) and 29 received Gemcitabine + nab-Paclitaxel (GEM + nab-PTX). Comparing the serum zinc concentrations before and after preoperative treatment, it was found to decrease after treatment with statistical difference (79.3 µg/dl vs. 68.7 µg/dl, p < 0.001). The result was consistent with the investigation for both the patients who received GEM + S1 and those who received GEM + nab-PTX (p = 0.019, p < 0.001, respectively). CONCLUSIONS: The preoperative chemotherapy consistently reduced the serum zinc concentrations in the PC patients, regardless of their regimen such as GEM + S1 and GEM + nab-PTX. Monitoring the serum zinc concentration and appropriate zinc supplementation may be essential for PC patients undergoing preoperative chemotherapy and pancreatectomy.

CA19-9 With Two-stage Resection Is Useful for Conversion Surgery in PDAC With Synchronous Oligometastases.

BACKGROUND/AIM: Pancreatic adenocarcinoma (PDAC) with synchronous oligometastases may indicate a surgical benefit after chemotherapy. We investigated whether primary and metastatic resection of PDAC with oligometastases can improve the survival and then explored prognostic factors to identify indications for conversion surgery. PATIENTS AND METHODS: We reviewed 425 patients with PDAC who underwent pancreatic resection from 2005 to 2019. Clinical characteristics and outcomes were analyzed. Two-stage resection was defined as preceding metastasectomy and subsequent primary resection after chemotherapy. RESULTS: Fifteen patients (3.5%) had synchronous oligometastases. We evaluated the overall survival of the patients with oligometastases and those without metastases. The survival curves almost completely overlapped (median survival time: 35.9 vs. 32.1 months). The univariate Cox regression analysis revealed a normal level of preoperative CA19-9 (p=0.075), two-stage resection (p=0.072), and R0 resection (p=0.064) were likely promising prognostic factors. The combination of a normal level of preoperative CA19-9 with two-stage resection was a significant prognostic factor (p=0.038). In addition, patients with a normal preoperative CA19-9 level and two-stage resection had better survival (46.1 vs. 28.1 months, p=0.026). CONCLUSION: The combination of normal preoperative CA19-9 with two-stage resection can be a useful way to identify patients with PDAC and oligometastases for surgical indication.

A case of an intramesenteric GIST accurately diagnosed and completely resected by PET-CT and laparoscopy after gastrectomy for gastric cancer.

We performed the accurate diagnosis and complete surgical resection of a gastrointestinal stromal tumor at the mesentery of the small bowel. Computed tomography (CT) in a 62-year-old man at 2 years after gastrectomy for gastric cancer showed a mesenteric tumor, with no other tumors noted. Positron emission tomography-computed tomography (PET-CT) showed a maximum standardized uptake value (SUV max) of 2.9 at the tumor. The presence of a single and low SUV max tumor allowed us to perform laparoscopic surgery. Partial resection of the tumor with an adequate margin was performed. The pathological findings showed c-kit positivity and a low Ki-67 proliferation index (<5%). In the present case, PET-CT and laparoscopic assessments were useful for accurately evaluating the surgical resectability of the mesenteric tumor after distal gastrectomy for gastric cancer. The low SUV max and laparoscopic findings led to complete surgical resection of a mesenteric tumor.

[Impact of Respiratory Motion on Point Doses for Three Whole-breast Irradiation Techniques after Breast-conserving Surgery].

PURPOSE: For whole-breast irradiation after breast-conserving surgery, computed tomography simulation (CTS) and irradiation are generally performed during free breathing. In treatment planning, there are three techniques: field-in-field (FIF), physical wedge (PW), and enhanced dynamic wedge (EDW). The aim of this study was to investigate the impact of respiratory motion on doses for these three irradiation techniques. METHODS: All doses were measured using an ionization chamber in a cylindrical phantom on a respiratory motion platform. Doses for each technique were measured with and without phantom motion. The dose without phantom motion was defined as the reference. The reference was compared to the dose with the phantom motion. The positions of the isocenter with respect to the ranges of phantom motion were set as exhale and intermediate. The phantom motion amplitude was set to 5 mm or 10 mm. The respiratory phase to initiate irradiation was varied as inhale, intermediate-inhale, exhale and intermediate-exhale. RESULTS: When the motion amplitude was 10 mm, the dose differences for the FIF, PW, and EDW techniques were 4.2%, 0.5%, and 0.8%, respectively, at the maximum. However, the dose difference for the FIF technique was -0.5% when the isocenter position was set to the intermediate phase of phantom motion. CONCLUSION: We found that the dose difference per fraction was reduced when the respiratory phase during CTS image acquisition was set to the intermediate phase. Meanwhile, the dose differences per fraction for the PW and EDW techniques were less affected by the respiratory motion.

Quantitatively assessed CT imaging measures of pulmonary interstitial pneumonia: effects of reconstruction algorithms on histogram parameters.

This study aimed the influences of reconstruction algorithm for quantitative assessments in interstitial pneumonia patients. A total of 25 collagen vascular disease patients (nine male patients and 16 female patients; mean age, 57.2 years; age range 32-77 years) underwent thin-section MDCT examinations, and MDCT data were reconstructed with three kinds of reconstruction algorithm (two high-frequencies [A and B] and one standard [C]). In reconstruction algorithm B, the effect of low- and middle-frequency space was suppressed compared with reconstruction algorithm A. As quantitative CT parameters, kurtosis, skewness, and mean lung density (MLD) were acquired from a frequency histogram of the whole lung parenchyma in each reconstruction algorithm. To determine the difference of quantitative CT parameters affected by reconstruction algorithms, these parameters were compared statistically. To determine the relationships with the disease severity, these parameters were correlated with PFTs. In the results, all the histogram parameters values had significant differences each other (p<0.0001) and those of reconstruction algorithm C were the highest. All MLDs had fair or moderate correlation with all parameters of PFT (-0.64

Effect of reconstruction algorithm on image quality and identification of ground-glass opacities and partly solid nodules on low-dose thin-section CT: experimental study using chest phantom.

PURPOSE: The purpose of this study was to assess the influence of reconstruction algorithm on identification and image quality of ground-glass opacities (GGOs) and partly solid nodules on low-dose thin-section CT. MATERIALS AND METHODS: A chest CT phantom including simulated GGOs and partly solid nodules was scanned with five different tube currents and reconstructed by using standard (A) and newly developed (B) high-resolution reconstruction algorithms, followed by visually assessment of identification and image quality of GGOs and partly solid nodules by two chest radiologists. Inter-observer agreement, ROC analysis and ANOVA were performed to compare identification and image quality of each data set with those of the standard reference. The standard reference used 120 mA s in conjunction with reconstruction algorithm A. RESULTS: Kappa values (kappa) of overall identification and image qualities were substantial or almost perfect (0.60