Two cases of gastric cancer with elevated serum levels of KL-6.

BACKGROUND: The serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6. CASE PRESENTATION: The first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml. CONCLUSIONS: These two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases.

A case report of adenosquamous carcinoma of the esophagogastric junction.

BACKGROUND: Many types of tumors can arise in the esophagogastric junction (EGJ). Squamous cell carcinoma (SCC) arising from the esophageal epithelia, adenocarcinoma arising from the gastric mucosa, or Barrett's esophageal mucosa are frequently observed in the EGJ. However, adenosquamous carcinoma (ASC) has been rarely observed in this area. We herein report a rare case of ASC of the EGJ. CASE PRESENTATION: An 81-year-old man visited our hospital complaining of dysphagia. Esophagogastroduodenoscopy detected an elevated tumor in the gastric cardia. Biopsy specimens taken from the tumor showed SCC. Computed tomography revealed a tumor located in the EGJ and node metastases surrounding the EGJ. The tumor was diagnosed as SCC, overhanging in the stomach, of the EGJ. The patient underwent a proximal gastrectomy with a lower esophagectomy and node dissection for the metastases surrounding the EGJ, and esophagogastrostomy in the lower mediastinum. Histopathologic examination showed the tumor consisted of SCC and adenocarcinoma. The adenocarcinoma consisted of nests scattered in the SCC. We observed adenocarcinoma component in 35% of the tumor and epithelial spread of SCC in the lower esophagus. Thus, we diagnosed the tumor as ASC of the EGJ. Eight metastatic nodes were dissected; both SCC and adenocarcinoma were observed in seven. CONCLUSIONS: In the present case, SCC may be originated from the squamous epithelia of the lower esophagus and grew into the stomach, and the adenocarcinoma may have differentiated from SCC through the infiltration.

Efficacy and Safety of 4 Fractions of Carbon-Ion Radiation Therapy for Hepatocellular Carcinoma: A Prospective Study.

INTRODUCTION: Prospective evidence supporting the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) remains lacking. This prospective study aimed to evaluate the safety and efficacy of hypofractionated C-ion RT in patients with HCC. METHODS: The inclusion criteria were as follows: (1) pathologically or clinically diagnosed HCC; (2) measurable tumor and tumor size ≤10 cm; (3) absence of major vascular invasion; (4) no extrahepatic metastasis; (5) the alimentary tract was not adjacent to the target lesion (>1 cm); (6) not suitable for or refusal to undergo surgery or local ablative therapies; (7) an interval ≥4 weeks from previous therapy; (8) no other intrahepatic lesion or at least 2 years after the previous curative therapy; (9) performance status score, 0-2; and (10) Child-Pugh score, 5-9. The prescribed C-ion RT dose was 52.8 Gy (relative biological effectiveness [RBE]) or 60.0 Gy (RBE) in 4 fractions. RESULTS: In total, 35 patients with HCC were enrolled between October 2010 and May 2016. The median follow-up durations in the survivor group (n = 23) and in the whole cohort were 55.1 and 49.0 months, respectively. The 2-, 3-, and 4-year overall survival rates were 82.8%, 76.7%, and 69.4%, respectively. The 2-, 3-, and 4-year local control (LC) rates were 92.6%, 76.5%, and 76.5%, respectively. The median time-to-progression was 25.6 months (95% confidence interval, 13.7-37.5 months). Grade 4 or 5 toxicities were not observed. Grade 3 acute and late toxicities were observed in 2 patients. There was no significant deterioration in serum albumin, bilirubin, prothrombin time-international normalized ratio, platelet count, or Child-Pugh score after C-ion RT. CONCLUSION: Four fractions of C-ion RT for HCC did not yield serious adverse events and showed promising LC, thus making it a safe and effective modality for this type of malignancy.

Basaloid Squamous Cell Carcinoma of the Uterine Cervix: Report of a Case With Molecular Analysis.

There is a lack of knowledge about molecular alterations in basaloid squamous cell carcinoma (BSCC) of the uterine cervix. A 72-year-old woman with a history of previous subtotal hysterectomy and current vaginal bleeding was referred to our hospital. Initially, adenoid cystic carcinoma (ACC) was diagnosed upon cervical cytology and biopsy. Chest imaging showed multiple metastatic lesions in both lungs. The surgical specimen showed BSCC with diffuse p16 immunoreactivity and negativity for S-100, c-kit, and neuroendocrine markers. There was a focal minor ACC component, which could have explained the previous cytology and biopsy diagnosis. Next-generation sequencing with two different panels showed coexisting PIK3CA mutation and NTRK2 fusion with 10 additional variants of unknown significance (ATR, DAXX, FAM123B, JAK1, KEL, MLL2, NOTCH2, PALB2, POLD1, POLE). The MYB gene fusions were not identified. The patient received chemotherapy with TRK inhibitor larotrectinib and carboplatin, which caused shrinkage of metastatic lung nodules. This is the first report of cervical BSCC with extensive molecular workup, which detected multiple genetic events, including targetable ones, which are potentially implicated in the development of a tumor. The accumulation of data and further studies on this tumor are necessary to define its diagnostic criteria and its clinical and biological behavior.

A case of gastric cancer that developed thrombocytopenia during treatment with nivolumab.

A 72-year-old man was treated by two-regimen chemotherapies for unresectable advanced gastric cancer with metastatic lymph nodes near the pancreatic head, followed by the third-line chemotherapy using nivolumab (Nivo). Ten days after the two-course Nivo chemotherapy, grade 4 thrombocytopenia (TCP) occurred according to the Common Terminology Criteria for Adverse Events. He was treated by steroid and Helicobacter pylori (HP) eradication therapies. Consequently, the platelet count improved rapidly without any complications. Before resuming the Nivo therapy, the platelet count was already improved. Fourth-line chemotherapy was then started using irinotecan. After three courses, his general condition worsened. Unfortunately, the patient died 18 months after gastric cancer diagnosis. Although rare, severe TCP is potentially a fatal complication of chemotherapy using immune checkpoint inhibitors. In addition to standard treatment with steroids, HP eradication therapy may be effective for Nivo-associated TCP.

Lung adenocarcinoma initially presenting as Trousseau's syndrome treated successfully with pembrolizumab: A case report.

A 60-year-old woman was urgently admitted to our hospital because of vertigo and left hemiplegia. Laboratory examination showed thrombocytopenia, high levels of D-dimer and carcinoembryonic antigen. Brain magnetic resonance imaging (MRI) revealed multiple bilateral cerebral infarctions. Chest computed tomography (CT) showed an irregularly shaped tumor in the upper lobe of the left lung and mediastinal node swelling. The histopathological findings revealed adenocarcinoma negative for anaplastic lymphoma kinase fusion gene, sensitive epidermal growth factor receptor mutations. A diagnosis of lung adenocarcinoma initially presenting as arterial thromboembolism was made, and she was treated with direct oral anticoagulant (DOAC). Subsequently, pembrolizumab therapy was initiated because tumor cells were positive for programmed cell death protein 1 (PD-L1;60%), and resulted in reduction of the tumor with normalization of the platelet count and d-dimer. The treatment has been continued for over one year without any recurrence of the disease or thromboembolism.

A feasibility study of high-dose hypofractionated carbon ion radiation therapy using four fractions for localized hepatocellular carcinoma measuring 3 cm or larger.

BACKGROUND AND PURPOSE: To evaluate the safety of carbon-ion radiotherapy (C-ion RT) using 60 Gy (relative biological effectiveness, RBE) in four fractions for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The primary outcome was acute toxicities within 90 days. The secondary outcomes were late toxicities, local control, and progression-free survival and overall survival rates. The key inclusion criteria were as follows: (1) 3 cm or larger HCC without major vascular invasion and not adjacent to the alimentary tract; (2) Child-Pugh's grade A/B; and (3) without extrahepatic metastasis. RESULTS: A total of 21 cases were analyzed between October 2012 and April 2016. The median follow-up period among the 17 survivors was 24.2 (range: 6.3-43.7) months. Grade 3 or higher acute toxicity was not observed, while three (14.3%) of the 21 patients experienced grade 3 late toxicities. The 1- and 2-year local control, progression-free survival, and overall survival rates were 100% and 92.3%, 81.0% and 50.0%, and 90.5% and 80.0%, respectively. CONCLUSION: C-ion RT using 60 Gy (RBE) in four fractions was safe and achieved promising local tumor control.

No Deterioration in Clinical Outcomes of Carbon Ion Radiotherapy for Sarcopenia Patients with Hepatocellular Carcinoma.

BACKGROUND/AIM: The relationship between sarcopenia and prognosis in carbon ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) has not yet been reported, therefore we analyzed the presence or absence of sarcopenia before C-ion RT as a prognostic factor for patients with HCC. PATIENTS AND METHODS: Data were retrospectively collected for patients who had undergone C-ion RT for HCC between September 2010 and December 2016. For defining the presence or absence of sarcopenia, skeletal muscles in the third lumbar vertebrae level were measured. Clinical outcomes were compared in the sarcopenia and non-sarcopenia groups. RESULTS: Of the 68 patients who were analyzed, 22 were classified into the sarcopenia and 46 into the non-sarcopenia groups. Median follow-up of patients was 33.5 months. The three-year overall survival (OS) rates in the sarcopenia and non-sarcopenia groups were 66% and 77%, respectively (p=0.51). CONCLUSION: Sarcopenia was not a prognostic factor for patients with HCC treated with C-ion RT, which was effective in HCC patients with sarcopenia without worsening the OS.

High incidence of other primary malignancies in patients with synchronous multiple gastric cancers "a multi-center retrospective cohort study".

This study evaluated the relationship between synchronous multiple gastric cancer and other primary malignancies. During 2002-2013, 1094 consecutive surgically treated gastric cancer patients were enrolled. Preoperatively, we performed total colonoscopy and whole-body computed tomography. When malignancies in other organs were suspected, detailed organ-specific examinations were performed. Synchronous multiple gastric cancer occurred in 102 patients (9.3%)which was frequently observed in patients with preoperative other primary malignancies (p < 0.001). Preoperative other primary malignancy was an independent risk factor for synchronous multiple gastric cancer (p = 0.001; hazard ratio: 2.145, 95% confidence interval: 1.354-3.399) and an independent prognostic factor of overall survival in patients undergoing gastrectomy with curative intent (p = 0.021; hazard ratio: 1.481, 95% confidence interval: 1.060-2.070). Thus, patients with preoperative other primary malignancies have a high risk of synchronous multiple gastric cancer. Careful preoperative examination is recommended to improve survival.

Carbon ion radiotherapy for 80 years or older patients with hepatocellular carcinoma.

BACKGROUND: To evaluate the safety and efficacy of carbon ion radiotherapy (C-ion RT) for 80 years or older patients with hepatocellular carcinoma (HCC). METHODS: Eligibility criteria of this retrospective study were: 1) HCC confirmed by histology or typical hallmarks of HCC by imaging techniques of four-phase multidetector-row computed tomography or dynamic contrast-enhanced magnetic resonance imaging; 2) no intrahepatic metastasis or distant metastasis; 3) no findings suggesting direct infiltration of the gastrointestinal tract; 4) performance status ≤2 by Eastern Cooperative Oncology Group classification; and 5) Child-Pugh classification A or B. Patients received C-ion RT with 52.8 Gy (RBE) or 60.0 Gy (RBE) in four fractions for usual cases and 60.0 Gy (RBE) in 12 fractions for close-to-gastrointestinal tract cases. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0). RESULTS: Between March 2011 and November 2015, 31 patients were treated. The median follow-up period of all patients was 23.2 months (range: 8.4-55.3 months). Median age at the time of registration of C-ion RT was 83 years (range: 80-95 years). Child-Pugh grade A and B were 27 patients and 4 patients, respectively. The 2-year estimated overall survival, local control, and progression-free survival rates were 82.3%, 89.2%, and 51.3%, respectively. No patients had Grade 2 or higher acute toxicities (within 3 months after C-ion RT). One patient experienced progression in Child-Pugh classification from A to B within 3 months after C-ion RT. In late toxicities, Grade 3 encephalopathy was observed in 3 patients, and 2 improved with medication. CONCLUSIONS: C-ion RT was effective with minimal toxicities for 80 years or older patients with hepatocellular carcinoma. TRIAL REGISTRATION: UMIN000020571 : date of registration, 14 January 2016, retrospectively registered.

A Modified Direct-Smear Processing Technique Employing Two-Step Centrifugation/Fixation Is Useful for Detecting High-Grade Urothelial Carcinoma.

OBJECTIVE: To demonstrate the usefulness of a direct-smear processing technique employing two-step centrifugation/fixation processing (TSCFP) in the cytoscreening of high-grade urothelial carcinoma (HGUC). STUDY DESIGN: Using the T24 HGUC cell line, we compared the cell yield and the morphological preservation of preparations concurrently processed by direct-smear, SurePath, ThinPrep, and TSCFP techniques. A total of 287 urine cytology cases subjected to TSCFP over a period of 6 years were reviewed and reclassified according to the Paris System for Reporting Urinary Cytology (PSRUC) and correlated with histology results. RESULTS: TSCFP of T24 cells demonstrated good cell yield with a recovery rate of about 70%. Diagnostic features of HGUC, such as a high nuclear/cytoplasmic ratio and irregular/hyperchromatic chromatin, were better discovered in TSCFP smears than in smears prepared with the other methods. Cytological evaluation of 287 voided urine specimens revealed that the rate of unsatisfactory preparations was quite low (0.30%) and the overall sensitivity, specificity, and positive and negative predictive values for urothelial carcinoma were 0.719, 0.923, 0.973, and 0.462, respectively. CONCLUSION: TSCFP was able to provide adequate preparations for detecting HGUC in urine cytology and could be considered as a promising processing method according to the principal purpose of PSRUC.

Fiducial marker matching versus vertebral body matching: Dosimetric impact of patient positioning in carbon ion radiotherapy for primary hepatic cancer.

PURPOSE: The aim of this study was to compare the dose-volume parameters of fiducial marker matching (MM) with vertebral body matching (VM) in patient positioning for carbon ion radiotherapy for primary hepatic cancer. MATERIALS AND METHODS: Twenty patients with primary hepatic cancer were retrospectively studied to assess changes in reproducibility of tumor position and dose distribution on two CT scans. One was for treatment planning and another was for dose confirmation, acquired the day before the first treatment day. The coverage of the clinical target volume (CTV) (D98) and normal liver volume excluding the CTV which received 20Gy relative biological effectiveness (RBE) (V20) were used as evaluation parameters. Additionally, the correlation of tumor movement and D98 was calculated in VM and MM. The prescription dose was 60.0Gy (RBE) delivered in four fractions (15Gy/fx). RESULTS: The median (range) D98 for VM and MM was 57.9 (20.8-59.9) and 59.9 (57.2-60.3) Gy (RBE), respectively. The median (range) V20 for VM and MM was 17.9 (4.8-44.4) and 16.2 (4.7-44.9) Gy (RBE), respectively. The D98 for MM was significantly larger than that for VM (p=0.001), although V20 showed no significant difference (p>0.05). Twelve patients were clinically acceptable (D98>57Gy (RBE)) with VM, while all patients were clinically acceptable with MM. Marker movement correlated with a decrease of D98 for VM (R=-0.814). CONCLUSION: Compared with VM, MM was clinically acceptable in all patients. This suggests that MM is more robust than VM.

Accordion phenomenon of the hepatic artery: mimicker of vasospasm or intimal injury.

The accordion phenomenon occurs because of mechanical distortion of a straightened vessel during coronary and vascular interventions. To date, however, this phenomenon has not been reported in vessels of the upper abdomen. We therefore describe the accordion phenomenon of the hepatic artery during transarterial chemoembolization seen while treating a liver tumor. As the accordion phenomenon is now known to involve hepatic arteries, it should be differentiated from vascular complications such as vasospasm or intimal injury.

Initial Results of Hypofractionated Carbon Ion Radiotherapy for Cholangiocarcinoma.

AIM: To report initial results of hypofractionated carbon ion radiotherapy (C-ion RT) for cholangiocarcinoma. PATIENTS AND METHODS: Data regarding seven patients with cholangiocarcinoma treated by C-ion RT were analyzed. Prescribed doses were 52.8 Gy [relative biological effectiveness (RBE)] or 60.0 Gy (RBE) in four fractions for intrahepatic cases and 12 fractions for hilar hepatic/close to gastro-intestinal tract cases. Local control and overall survival were evaluated and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up period was 16 months. There were two patients with stage I cancer, one with stage II, one with stage III, and three with stage IVA. Local control was achieved in five out of seven patients (71%) and survival was maintained in six out of seven patients (86%). There were no occurrences of acute or late toxicity of grade 3 or higher. CONCLUSION: Initial results show that hypofractionated C-ion RT appears to be tolerated and effective for cholangiocarcinoma.

New Method of Parent Catheter Advancement in the Balloon Anchor Technique during Balloon-Occluded Transarterial Chemoembolization for Hepatic Tumors.

Balloon-occluded transarterial chemoembolization (B-TACE) using a microballoon catheter is a promising method for improvement of lipiodol emulsion accumulation and local control relative to conventional transarterial chemoembolization. This method has been referred to as the balloon anchor technique in previous reports. We report a new technique for successful parent catheter advancement for achievement of stable backup for the selective insertion of a microballoon catheter during B-TACE using the microballoon as an anchor, even in patients with tortuous anatomy of the hepatic and celiac arteries. Deep cannulation of parent catheters was accomplished in all three cases and complications such as vascular injury were not observed in the postprocedure angiograms.

Transcatheter arterial embolization with N-butyl cyanoacrylate for arterial esophageal bleeding in esophageal cancer patients.

BACKGROUND: The aim of this study is to evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for the treatment of arterial esophageal bleeding in esophageal cancer patients. METHODS: Between November 2008 and December 2014, five esophageal cancer patients underwent TAE with NBCA for the treatment of arterial esophageal bleeding. We retrospectively evaluated the technical and clinical success, recurrent bleeding, and procedure-related complications. RESULTS: All of the patients had bleeding from the esophageal artery and were in shock at the beginning of TAE. Four patients had a coagulopathy at the time of TAE; however, the TAE could successfully arrest bleeding in all five patients. After TAE, they immediately recovered from the shock state. Two patients were discharged without event, one patient is currently hospitalized for another complication, and the other two patients died due to multiorgan failure. In addition, no procedure-related complications such as esophageal infarction and recurrence of arterial esophageal bleeding were observed during this study. CONCLUSIONS: TAE with NBCA can arrest bleeding in esophageal cancer patients with active arterial esophageal bleeding, even in those with a pre-existing coagulopathy.

Massive hemothorax due to inferior phrenic artery injury after blunt trauma.

Injury to the inferior phrenic artery after blunt trauma is an extremely rare event, and it may occur under unanticipated conditions. This case report describes an injury to the left inferior phrenic artery caused by blunt trauma, which was complicated by massive hemothorax, and treated with transcatheter arterial embolization (TAE). An 81 year-old female hit by a car while walking at the traffic intersection was transferred to the emergency department, computed tomography scanning revealed active extravasations of the contrast medium within the retrocrural space and from branches of the internal iliac artery. The patient underwent repeated angiography, and active extravasation of contrast medium was observed between the retrocrural space and the right pleural space originating from the left inferior phrenic artery. The injured left inferior phrenic artery was successfully embolized with N-butyl cyanoacrylate, resulting in stabilization of the patient's clinical condition. Inferior phrenic artery injury should be recognized as a rare phenomenon and causative factor for hemothorax. TAE represents a safe and effective treatment for this complication and obviates the need for a thoracotomy.

Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to compare carbon ion radiotherapy (C-ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing. METHODS: Data of 10 patients who were treated using C-ion RT with a total dose of 60 Gy(RBE) in four fractions were used. The virtual plan of SBRT was simulated on the treatment planning computed tomography images of C-ion RT. Dose volume parameters such as minimum dose covering 90% of the planning target volume (PTV D90), homogeneity index (HI), conformity index (CI), mean liver dose (MLD), volume of the liver receiving 5 to 60 Gy (V5-60), and max point dose (Dmax) of gastrointestinal (GI) tract were calculated from both treatment plans. RESULTS: The PTV D90 was 59.6 ± 0.2 Gy(RBE) in C-ion RT, as compared to 56.6 ± 0.3 Gy in SBRT (p < 0.05). HI and CI were 1.19 ± 0.03 and 0.79 ± 0.06, respectively in C-ion RT, as compared to 1.21 ± 0.01 and 0.37 ± 0.02, respectively in SBRT. Only CI showed a significant difference between two modalities. Mean liver dose was 8.1 ± 1.4 Gy(RBE) in C-ion RT, as compared to 16.1 ± 2.5 Gy in SBRT (p < 0.05). V5 to V50 of liver were higher in SBRT than C-ion RT and significant differences were observed for V5, V10 and V20. Dmax of the GI tract was higher in SBRT than C-ion RT, but did not show a significantly difference. CONCLUSIONS: C-ion RT provides an advantage in both target conformity and normal liver sparing compared with SBRT.