Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for locally recurrent rectal cancer: Japan Clinical Oncology Group study JCOG1801 (RC-SURVIVE study).

A randomized phase III trial was initiated in Japan in August 2019 to confirm the superiority of preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy compared to the standard treatment, i.e. surgery plus adjuvant chemotherapy, for locally recurrent rectal cancer in local relapse-free survival. In all, 110 patients from 43 Japanese institutions will be recruited over a period of 6 years. Eligible patients would be registered and randomly assigned to each group with an allocation ratio of 1:1. The primary endpoint is local relapse-free survival. The secondary endpoints are overall survival, relapse-free survival, proportion of local relapse, proportion of distant relapse, proportion of patients with pathological R0 resection, response rate of preoperative chemoradiotherapy (preoperative chemoradiotherapy arm), pathological complete response rate (preoperative chemoradiotherapy arm), proportion of patients who completed the protocol treatment, incidence of adverse events (adverse reactions) and quality of life after surgery. This trial has been registered at the Japan Registry of Clinical Trial: jRCTs031190076 [https://jrct.niph.go.jp/latest-detail/jRCTs031190076] and ClinicalTrials.gov: NCT04288999 [https://clinicaltrials.gov/ct2/show/NCT04288999].

A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002.

BACKGROUND: Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose. METHODS: Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1, S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %. RESULTS: Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52). CONCLUSIONS: Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

Evaluation of 64-Channel Contrast-Enhanced Multi-detector Row Computed Tomography for Preoperative N Staging in cT2-4 Gastric Carcinoma.

BACKGROUND: Preoperative N staging is essential for the best treatment planning in patients with gastric carcinoma. The aim of this study was to evaluate the accuracy of preoperative N staging using contrast-enhanced multi-detector row computed tomography (CE-MDCT) in patients with resectable cT2-4 gastric carcinoma. METHODS: A total of 218 patients who underwent a gastrectomy with D2 lymphadenectomy for previously untreated cT2-4 primary gastric carcinoma were studied. Preoperative N staging was performed according to the 7th (UICC) TNM Staging System using pre-specified criteria on a 64-channel CE-MDCT and was compared with postoperative pathologic N staging. RESULTS: In all 218 patients, a distal or total gastrectomy was performed. The overall accuracy of the preoperative N staging was 46.3% (101/218), with the proportion of over- and under-staging being 26.6% (58/218) and 27.1% (59/218), respectively. The sensitivity, specificity, and accuracy for lymph node metastasis (≥pN1) were 79.1% (106/134), 50.0% (42/84), and 67.9% (148/218), respectively. The sensitivity, specificity, and accuracy for multiple lymph node metastases (≥pN2) were 80.2% (73/91), 68.5% (87/127), and 73.4% (160/218), respectively. Multivariate analyses showed that macroscopic type 2 and ≥6 cm-sized tumors were associated with preoperative over-N staging, while macroscopic type 1/3 tumors were associated with under-N staging. CONCLUSION: Preoperative N staging with pinpoint accuracy is difficult. However, CE-MDCT offers a reasonably high sensitivity and specificity for ≥pN2 and may be useful for selecting candidates for neoadjuvant therapies. The macroscopic type and size of the primary tumor may affect the accuracy of preoperative N staging.

Histopathological characteristics of hypervascular cholangiocellular carcinoma as an early stage of cholangiocellular carcinoma.

AIM: Prognosis of hypervascular cholangiocellular carcinoma (h-CCC) is reportedly better than that of ordinary hypovascular CCC (o-CCC). The aim of this study is to clarify the histopathological characteristics of h-CCC. METHODS: On the basis of the findings in the arterial phase of contrast-enhanced computed tomography, 16 cases of mass-forming-type CCC were divided into two groups (h-CCC, n = 8; o-CCC, n = 8). Areas of high (Area H-a) and low (Area H-b) attenuation in h-CCC cases and areas of low attenuation in o-CCC cases (Area O) were delineated. These areas were then evaluated histopathologically to determine the proportion of tumor cells, fibrous stroma, arterial vessel density, and immunohistochemical expression of Vascular endothelial growth factor; angiopoietin-2; cytokeratin 7, CK19, SOX9 and SOX17 genes; epithelial cell adhesion molecule; and the Bmi-1, Ki-67, epithelial membrane antigen and polyclonal carcinoembryonic antigen. RESULTS: The areal ratio of tumor cells decreased and that of fibrous stroma increased in the following order: Area H-a, Area H-b and Area O. Values for AVD and neural cell adhesion molecule positivity rate were significantly higher in Area H-a than in Areas H-b or O. Expressions of vascular endothelial growth factor and angiopoietin-2 were significantly higher in Areas H-a and H-b than in Area O. The Ki-67 labeling index increased in the following order: Area H-a, Area H-b and Area O. CONCLUSION: A high areal ratio of tumor cells and AVD as well as a high expression of stem cells and angiogenic markers were observed in cases of h-CCC, whereas the areal ratio of fibrous stroma and malignant potential were low. These results suggest that h-CCC may represent the early stage of CCC.

Early venous return in hepatic angiomyolipoma due to an intratumoral structure resembling an arteriovenous fistula.

Early venous return (EVR) is an important radiological feature of hepatic angiomyolipoma (HAML) that can aid in differential diagnosis, but the pathogenic mechanisms of EVR have yet to be elucidated. We present the first HAML case for which a probable mechanism for EVR is described. The patient was a 46-year-old woman, who had a growing 6-cm tumor with EVR in segment 3 of the liver as revealed by dynamic contrast-enhanced computed tomography. Left hepatic lobectomy was performed to prevent tumor rupture. Histopathological and immunohistochemical analyses of the excised tumor indicated HAML. Successive microsections of the tumor were stained with hematoxylin-eosin and Victoria blue to visualize the vascular structure within and around the tumor. These analyses led to three major findings. First, many well-defined thick-walled vessels, such as arteries, were found entering the tumor. Second, many thick-walled vessels within the tumor were connected directly to thin-walled vessels, resembling arteriovenous fistulae. Finally, thin-walled intratumoral vessels were connected directly to the hepatic vein. These histological findings suggested that the rich arterial flow into the tumor was being rapidly drained into the hepatic vein through intratumoral arteriovenous connections. We also detected these same anomalous circulatory pathways in tissue sections from three of four additional HAML cases with EVR. Aberrant arteriovenous fistulae within the tumor may account for many cases of EVR in HAML patients.

Treatment of hepatocellular carcinoma with a portal vein tumor thrombus and pulmonary metastases of rectal cancer with microsatellite stability using atezolizumab plus bevacizumab.

Herein, we report the successful treatment using atezolizumab plus bevacizumab of a patient with hepatocellular carcinoma (HCC) with a portal vein tumor thrombus and multiple pulmonary metastases from rectal cancer with microsatellite stability. This patient developed rectal cancer with synchronous pulmonary metastases and HCC. After resecting the primary lesion of the rectal cancer, transcatheter arterial chemoembolization was performed for the HCC. Drug therapy was planned for multiple pulmonary metastases of rectal cancer; however, the early development of recurrent HCC with portal vein tumor thrombus had to be highly prioritized, and atezolizumab plus bevacizumab was introduced. Following the disappearance of the recurrent HCC lesion, the metastatic pulmonary nodules shrunk into scar-like spots. The treatment for both HCC and pulmonary metastases of rectal cancer were considered to result in clinical complete response.

Difficult removal of totally implantable venous access devices in adult patients: Incidence, risk factors, and management.

BACKGROUND: Totally implantable venous access devices (TIVADs) have played an important role of medical oncology practice. However, operators sometimes encounter considerable difficulty when removing TIVADs. This study aimed to investigate the incidence of difficult TIVAD removal, determine associated risk factors, and investigate interventional radiology (IR) approaches to difficult removal. METHODS: A total of 514 TIVAD removal procedures performed in a single-center between January 2014 and May 2021 were retrospectively analyzed to determine incidence of difficult removal and associated risk factors. IR approaches applied in difficult removal cases were also reviewed. RESULTS: The incidence of difficult removal was 7.4% (38/514). In univariable analysis, indwelling duration, silicone catheter, and subcutaneous leakage of fluid were identified as significant risk factors for difficult removal. Multivariable analysis showed that indwelling duration per year (odds ratio (OR), 1.46; 95% confidence interval (CI), 1.28-1.67; p < 0.01) and subcutaneous leakage of fluid (OR, 6.04; 95% CI, 2.45-14.91; p < 0.01) were significantly associated with difficult removal. In the 38 difficult removal cases, 32 TIVADs could be removed using more dissection and traction than the standard removal method. In the other 6, TIVADs were successfully removed by using several IR techniques, including insertion of a guide wire (n = 1), dissection using an introducer sheath (n = 2), pushing with a dilator (n = 1), and pulling with a snare (n = 2). CONCLUSION: Difficult TIVAD removal is uncommon. However, operators should expect it when removing long indwelling TIVADs and those with subcutaneous leakage. IR approaches to difficult removal are minimally invasive and can be useful.

Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dual-energy CT.

PURPOSE: To evaluate the clinical usefulness of dual-energy computed tomography (CT) with weighted-average (WA) images and iodine overlay (IO) images in the evaluation of laryngeal cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written comprehensive consent was obtained from all patients. Seventy-two consecutive patients underwent 128-section dual-source dual-energy CT to stage laryngeal (n=27) or hypopharyngeal (n=45) cancer. Three observers who were blinded to the patients' clinical histories and histopathologic findings evaluated cartilage invasion on WA images alone or in combination with IO images (nonossified cartilages were selectively evaluated on IO images) by using a five-point scale. Thirty of the 72 patients (42%) underwent surgery, and findings from histopathologic examination in those patients were used as the standard of reference for the evaluation of diagnostic performance with receiver operating characteristic (ROC) curve analysis and in terms of sensitivity and specificity. Interobserver reproducibility was calculated with κ statistics. RESULTS: For thyroid cartilage, the area under the ROC curve (AUC) of the WA plus IO images was marginally larger than that for WA images alone (AUC=0.957 vs 0.870, respectively; P=.075). The specificity of WA plus IO images was significantly superior to that of WA images alone (96% vs 70%, respectively; P=.031), with no compromise to the sensitivity (86% for both). For thyroid and cricoid cartilages, the interobserver reproducibility was higher for diagnoses made with WA plus IO images (κ=0.68-0.72 and 0.64-0.79, respectively) than for those made with WA images alone (κ=0.29-0.56 and 0.20-0.64, respectively). CONCLUSION: Combined analysis of WA and IO images obtained with dual-energy CT improves the diagnostic performance and interobserver reproducibility of evaluations of laryngeal cartilage invasion by SCC.

Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms.

OBJECTIVES: We investigated the detectability of somatostatin receptor scintigraphy (SRS) for neuroendocrine neoplasms (NEN). METHODS: From January 2016 to October 2020, 125 SRS examinations using indium-111 pentetreotide performed for patients with NEN lesions were retrospectively evaluated. The detection rate of NEN lesions was determined according to histopathological classification by primary site and by organ. RESULTS: At least one NEN lesion was detected in 73% (91/125) with a positive Krenning score of ≥2 in SRS. The detection of abdominal NENs (gastrointestinal tract, 38; pancreas, 62; and others, 14) was 89% (49/55) for neuroendocrine tumor (NET)-grade (G) 1, 78% (32/41) for NET-G2, 66% (2/3) for NET-G3, 31% (4/13) for neuroendocrine carcinoma (NEC), 100% (1/1) for mixed neuroendocrine-non-neuroendocrine neoplasm, and 0% (0/1) for non-classified NEN. That of thoracic NENs was 33% (2/6) for typical carcinoid tumor and 40% (2/5) for atypical carcinoid tumor. For a total of 226 organ lesions, hepatic lesions were 76% (58/76); pancreatic lesions, 61% (31/51); lymph node lesions, 77% (27/35); bone lesions, 83% (20/24); duodenal lesions, 82% (9/11); and other lesions, 41% (11/27). CONCLUSION: The detectability of SRS for NEN in Japan was verified at a center, and its usefulness was confirmed.

Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment.

The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into "effective" and "non-effective" groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five "effective" cases and all four (100%) "non-effective" cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC.

Long-term recurrence-free survival in a patient with primary hepatic carcinosarcoma: case report with a literature review.

A 72-year-old man was found to have a 40 mm mass in liver segment VIII during follow-up abdominal ultrasonography for type C viral hepatitis. Abdominal ultrasound showed a well-defined mass containing a cystic component, and computed tomographic hepatic arteriography showed heterogeneous enhancement except for cystic necrosis. Under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC), partial resection of liver segment VIII was performed. The encapsulated tumor consisted of a peripheral solid component with a central necrotic area. Histologically, the solid component had a two-layer structure, an HCC component in the external area and a sarcomatous component with neoplastic osteoid formation in the internal area, showing histological transition. Immunohistochemically, the HCC component was positive for hepatocyte antigen and negative for vimentin. The Ki-67 labeling index was found to increase from 5% to 58% with increasing histologic atypia. The sarcomatous component was positive for vimentin and negative for pan-keratin and hepatocyte antigen, with a Ki-67 labeling index of >90%. These findings led to a diagnosis of primary hepatic carcinosarcoma. Although previously reported patients with hepatic carcinosarcoma showed early metastasis with a very poor outcome, this patient has remained free of recurrence for 30 months, which is the longest recurrence-free survival time recorded for this type of cancer. Since relatively early-stage hepatic carcinosarcoma rarely seems to present as a small tumor showing a concentric growth pattern, we report this case with a review of the literature.

Solitary hepatic lymphangioma: report of a case.

A 52-year-old woman presented with upper abdominal pain. Abdominal ultrasonography showed a 4-cm well-defined mass containing solid and cystic components in segment IV of the liver, and contrast-enhanced T1-weighted magnetic resonance imaging revealed heterogeneous enhancement within the tumor, indicating a solid or fibrous component. There were no cystic lesions in any other organs. A partial hepatectomy was performed, based on a preoperative diagnosis of sclerosing hemangioma and biliary cystadenoma or cystadenocarcinoma. Pathologically, the tumor appeared to be a multilocular and cystic lesion lined by attenuated endothelial- like cells with no atypia. Immunohistochemistry demonstrated the endothelial-like cells to be positive for the lymphatic-specific markers D2-40, LYVE-1, and Prox-1, which proved helpful for confirming the diagnosis as solitary hepatic lymphangioma. This case is presented with details of the pathologic and radiologic findings, because solitary hepatic lymphangioma is an extremely rare tumor and no previous reports have provided details of the immunohistochemical characteristics.

Clinical Outcomes and Techniques for Radiofrequency Ablation of Lung Tumors Smaller than 1 cm.

Purpose: To evaluate the outcomes of radiofrequency ablation (RFA) on lung tumors < 1 cm in maximum diameter. Materials and Methods: Twenty-eight patients (12 male, 16 female; median age, 59 years; mean age, 58 ± 16 years; range, 16-78 years) who underwent RFA for lung tumors < 1 cm in diameter between November 2009 and September 2018 were included in this study. Thirty-five tumors (median size, 8.4 mm; mean size, 7.7 ± 1.9 mm; range, 3.6-9.9 mm) were treated with 33 sessions of RFA. Technique efficacy and safety were subsequently evaluated. Initial and secondary technique efficacy were defined as complete ablation without residual tumor or local tumor progression after initial and repeat RFA, respectively. Safety was evaluated according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Residual tumor remained for 1 tumor (3%, 1/35) and local tumor progression was found in 2 tumors (6%, 2/35). Initial technique efficacy rate was therefore 91% (32/35). The remaining 3 tumors were treated by repeat RFA (secondary technique efficacy rate: 100%, 35/35). Initial technique efficacy rate was significantly lower for tumors treated with starting energy ≥ 20 W (P = 0.02) and showing a quick increase in tissue impedance (P = 0.01). There were 4 grade 2 adverse events (12%, 4/33) comprising pneumothorax requiring chest tube placement, and 14 grade 1 adverse events comprising self-limiting pneumothorax (36%, 12/33) and pulmonary parenchymal hemorrhage (6%, 2/33). Conclusion: To achieve good outcomes for lung tumors < 1 cm, radiofrequency energy should be started at < 20 W. Application of manual mode ablation might be considered when delivery of power cannot be continued due to a quick increase in tissue impedance.

[New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].

This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.

Adenocarcinoma and neuroendocrine tumor arising within presacral teratoma associated with Currarino syndrome: A case report.

We present a case of a 59-year-old woman with a malignant tumor arising within presacral teratoma associated with Currarino syndrome (CS). A characteristic crescent-shaped sacrum was detected on preoperative image examination and the presacral mass was pathologically diagnosed as a malignant tumor associated with CS. To our knowledge, this is the first case report of presacral teratoma associated with CS coexisting with both adenocarcinoma and a neuroendocrine tumor.

Evaluation of the degree of pancreatic fatty infiltration by area-based assessment of CT images: comparison with histopathology-based and CT attenuation index-based assessments.

PURPOSE: The purpose of this study was to evaluate the degree of fatty infiltration (FI) of the pancreas using area-based assessment on computed tomography (CT) (CT area-based assessment) in its correlation and agreement/concordance with histopathology-based assessment. Furthermore, we examined whether CT area-based assessment was better than CT attenuation index-based assessment. MATERIALS AND METHODS: We retrospectively evaluated the degree of FI of the pancreas in 37 pancreatic cancer patients who had undergone preoperative CT and pancreaticoduodenectomy. The degree of FI of the pancreas was examined by histopathology-based assessment using surgical resection samples, and CT area-based and CT attenuation index-based assessments. RESULTS: Mean values of pancreatic FI measured by area-based assessment on unenhanced CT and by histopathology-based assessments were 14.4 ± 23.2 % (range 0-77.7 %) and 16.2 ± 17.4 % (range 0.2-60.2 %), respectively. Area-based assessment on unenhanced CT showed higher correlation and concordance with histopathology-based assessment, demonstrating a Spearman correlation coefficient of 0.78 (P < 0.0001) and a Kendall's tau-b coefficient of 0.69 (P < 0.0001). For CT attenuation index-based assessment, the corresponding values were -0.66 (P < 0.0001) and -0.39 (P = 0.008), respectively. CONCLUSIONS: To order/categorize subjects according to the degree of FI of the pancreas, CT area-based assessment is suggested to be better than CT attenuation index-based assessment.

Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.

A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.