Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture.

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II-III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II-III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II-III NSCLC in the real-world setting.

[Solitary lymph node metastasis from early-stage hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation: a case report and review of the Japanese literature].

A 77-year-old man with chronic hepatitis C underwent transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC) in segment 8 of the liver. Necrosis was confirmed radiologically. After 19 months, recurrent HCC in segment 6 was treated with TACE and RFA. There was no recurrence. Direct-acting antiviral (DAA) therapy 24 months after the initial procedure led to a sustained virologic response. AFP-L3 markedly increased 11 months after DAA therapy, and MRI 6 months after that showed a solitary lymph node near the common bile duct. Because no intrahepatic recurrence or other lymph nodes were seen, the solitary node was excised. Histopathology showed metastatic HCC. There has been no subsequent recurrence over 13 months of follow-up.

The management of tumor motions in the stereotactic irradiation to lung cancer under the use of Abches to control active breathing.

PURPOSE: Breathing control is crucial to ensuring the accuracy of stereotactic irradiation for lung cancer. This study monitored respiration in patients with inoperable nonsmall-cell lung cancer using a respiration-monitoring apparatus, Abches, and investigated the reproducibility of tumor position in these patients. METHODS: Subjects comprised 32 patients with nonsmall-cell lung cancer who were administered stereotactic radiotherapy under breath-holding conditions monitored by Abches. Computed tomography (CT) was performed under breath-holding conditions using Abches (Abches scan) for treatment planning. A free-breathing scan was performed to determine the range of tumor motions in a given position. After the free-breathing scan, Abches scan was repeated and the tumor position thus defined was taken as the intrafraction tumor position. Abches scan was also performed just before treatment, and the tumor position thus defined was taken as the interfraction tumor position. To calculate the errors, tumor positions were compared based on Abches scan for the initial treatment plan. The error in tumor position was measured using the BrainSCAN treatment-planning device, then compared for each lung lobe. RESULTS: Displacements in tumor position were calculated in three dimensions (i.e., superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) dimensions) and recorded as absolute values. For the whole lung, average intrafraction tumor displacement was 1.1 mm (L-R), 1.9 mm (A-P), and 2.0 mm (S-I); the average interfraction tumor displacement was 1.1 mm (L-R), 2.1 mm (A-P), and 2.0 mm (S-I); and the average free-breathing tumor displacement was 2.3 mm (L-R), 3.5 mm (A-P), and 7.9 mm (S-I). The difference between using Abches and free breathing could be reduced from approximately 20 mm at the maximum to approximately 3 mm in the S-I direction for both intrafraction and interfraction positions in the lower lobe. In addition, maximum intrafraction tumor displacement with the use of Abches was 4.5 mm (S-I) in the lingular segment. These results suggest that use of the Abches system can reduce deviations in tumor position to levels below those achieved under free breathing, irrespective of the tumor location. CONCLUSIONS: Respiratory control with high accuracy and reproducibility is required for high-precision radiotherapy of inoperable nonsmall-cell lung cancer and was achieved using Abches in this study.

Meta-analysis of laparoscopy-assisted and open distal gastrectomy for gastric cancer.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is a minimally invasive technique. We performed a meta-analysis of five randomized clinical trials (RCTs) to evaluate and compare the benefits of LADG with those of open distal gastrectomy (ODG). METHODS: The present meta-analysis was based on the comparison of LADG with ODG for gastric cancer. The following factors were examined: operative time, estimated blood loss, number of harvested lymph nodes, time to resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. RESULTS: We selected five RCTs to compare LADG with ODG for gastric cancer. A total of 326 patients with gastric cancer were included in this meta-analysis of whom 164 underwent LADG and 162 underwent ODG. There was a significant difference in the volume of intraoperative blood loss, period of hospital stay, frequency of analgesic administration, and rate of complications between LADG and ODG. There was no difference in the resumption of oral intake, rate of tumor recurrence, and mortality. The operative time was significantly longer and the number of harvested lymph nodes was significantly smaller in LADG than in ODG. CONCLUSION: LADG is significantly superior to ODG regarding the volume of blood loss, duration of hospital stay, level of pain, and risk of complications. There was no difference in the resumption of oral intake, rate of tumor recurrence, and mortality. However, LADG was significantly inferior to ODG regarding operative time and also had a smaller number of harvested lymph nodes.

A meta-analysis of randomized controlled trials that compared laparoscopy-assisted and open distal gastrectomy for early gastric cancer.

BACKGROUND: We conducted a meta-analysis to evaluate and compare the advantages of laparoscopy-assisted distal gastrectomy (LADG) over open distal gastrectomy (ODG) for treating early gastric cancer (EGC). METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and January 2010 by using the following search terms: laparoscopy-assisted gastrectomy, laparoscopic gastrectomy, and early gastric cancer. The following data were analyzed: operative time, estimated blood loss, number of harvested lymph nodes, time required for resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. RESULTS: We selected four papers reporting randomized control studies (RCTs) that compared LADG with ODG for EGC. Our meta-analysis included 267 patients with EGC; of these, 134 and 133 had undergone LADG and ODG, respectively. The volume of intraoperative blood loss, frequency of analgesic administration, and rate of complications were significantly lesser for LADG than for ODG. However, the time required for resumption of oral intake and duration of hospital stay did not significantly differ between LADG and ODG. The operative time for LADG was significantly longer than that for ODG; further, the number of harvested lymph nodes was significantly lesser in the LADG group than in the ODG group. CONCLUSION: LADG is advantageous over ODG because it results in lesser blood loss, is less painful, and is associated with a low risk of complications. Additional RCTs that compare LADG and ODG and investigate the long-term oncological outcomes of LADG are required to determine the advantages of LADG over ODG.

Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats.

OBJECTIVE AND DESIGN: The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats. MATERIALS AND TREATMENT: Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 microg/g) was administered intravenously to the control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of saline to the sham group. METHODS: The O(2)(-*) generated was measured as the current in the right atrium using an electrochemical O(2)(-*) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration. RESULTS: The O(2)(-*) current increased in the control group and was significantly attenuated in the UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in the UTI group. CONCLUSIONS: UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion.

We recently reported that excessive superoxide anion radical (O(2)(-)) was generated in the jugular vein during reperfusion in rats with forebrain ischemia/reperfusion using a novel electrochemical sensor and excessive O(2)(-) generation was associated with oxidative stress, early inflammation, and endothelial injury. However, the source of O(2)(-) was still unclear. Therefore, we used allopurinol, a potent inhibitor of xanthine oxidase (XO), to clarify the source of O(2)(-) generated in rats with forebrain ischemia/reperfusion. The increased O(2)(-) current and the quantified partial value of electricity (Q), which was calculated by the integration of the current, were significantly attenuated after reperfusion by pretreatment with allopurinol. Malondialdehyde (MDA) in the brain and plasma, high-mobility group box 1 (HMGB1) in plasma, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma were significantly attenuated in rats pretreated with allopurinol with dose-dependency in comparison to those in control rats. There were significant correlations between total Q and MDA, HMGB, or ICAM-1 in the brain and plasma. Allopurinol pretreatment suppressed O(2)(-) generation in the brain-perfused blood in the jugular vein, and oxidative stress, early inflammation, and endothelial injury in the acute phase of forebrain ischemia/reperfusion. Thus, XO is one of the major sources of O(2)(-)- in blood after reperfusion in rats with forebrain ischemia/reperfusion.

A case of mesenteric lymphadenitis with long-acting symptom, showing marked response to corticosteroid.

A 17-year-old girl who had right lower abdominal pain with multiple swelling of lymph nodes in the ileocecal region and she was admitted to a neighboring hospital. Since there was no improvement of condition with antibiotic resistance, we were consulted. Lymph node biopsy under laparoscopy demonstrated nonspecific findings. She then developed erythema nodosum, suggesting the presence of autoimmune etiology. Treatment with systemic corticosteroid resulted in symptomatic improvement. Mesenteric lymphadenitis like this case is rare.

Penetrating atherosclerotic ulcer in the juxtarenal abdominal aorta and coronary artery disease: emergency one-stage repair with off-pump coronary surgery.

An 82 year-old woman suddenly developed severe back pain. Enhanced computed tomography and aortography revealed penetrating atherosclerotic ulcer (PAU), that was a localized contrast-filled outpouching in the juxtarenal abdominal aorta and intramural hematoma within the aortic wall. Coronary angiography revealed significant stenosis in the left anterior descending artery and right coronary artery. Urgent aortic repair was required; therefore we performed the combined operations of coronary artery bypass grafting and aortic repair. PAUs typically occur in elderly patients with a history of hypertension, and are frequently complicated by coronary artery disease. However, few cases have been reported in the literature, such as cases involving combined operations. In this study, we report on a successful case of emergency repair involving concomitant juxtarenal abdominal aortic replacement for PAU and off-pump coronary artery bypass grafting.

Two-dimensional electrophoresis database of fluorescence-labeled proteins of colon cancer cells.

We constructed a novel database of the proteome of DLD-1 colon cancer cells by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of fluorescence-labeled proteins followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis. The database consists of 258 functionally categorized proteins corresponding to 314 protein spots. The majority of the proteins are oxidoreductases, cytoskeletal proteins and nucleic acid binding proteins. Phosphatase treatment showed that 28% of the protein spots on the gel are phosphorylated, and mass spectrometric analysis identified 21 of them. Proteins of DLD-1 cells and of laser-microdissected colon cancer tissues showed similar distribution on 2D gels, suggesting the utility of our database for clinical proteomics.

Treatment planning of stereotactic radiotherapy for solitary lung tumor.

PURPOSE: To analyze the stereotactic radiotherapy (SRT) plans in terms of internal target volume (ITV) and organs at risk (OARs). METHODS AND MATERIALS: Treatment planning and dose distributions were analyzed using dose-volume histograms (DVHs) of ITV and OARs in 37 patients, who were treated for a solitary lung tumor with SRT. The stereotactic body frame (SBF) was used for immobilization and accurate setup. Prescription dose was 48 Gy in four fractions at the isocenter. RESULTS: Use of SBF limits the extent of the noncoplanar beam directions to prevent a collision with the Linac gantry. DVH analyses showed that the homogeneity index, defined as the ratio of maximum and minimum dose to ITV, ranged from 1.03 to 1.25 (mean, 1.12). The volume irradiated with 20 Gy or more (V(20)) of the lung ranged from 0.3 to 11.6% (mean, 4.4%) of the whole lung volume. The maximum dose to the other OARs ranged from 0 to 11.8 Gy (mean, 0.5-2.7) per fraction. No clinically significant complications were encountered. CONCLUSIONS: Despite the limitation of the beam arrangement, a homogeneous target dose distribution, while avoiding high doses to normal tissues, was obtained.

Usefulness of one-stage coronary artery bypass grafting on the beating heart and abdominal aortic aneurysm repair.

Abdominal aortic aneurysm (AAA) is commonly associated with coronary artery disease (CAD). Simultaneous coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under cardiac arrest and AAA repair may be considerably invasive. Recently CABG under the beating heart without CPB has been reported as a less invasive method. We report the combined operation of CABG on a beating heart and AAA repair for AAA patients with CAD, and compare it with a separate operation. A retrospective review of the records of consecutive patients who underwent elective combined procedure or single operation for CABG on a beating heart and/or repair of the AAA between May 1999 and October 2001 was carried out. Ten patients underwent combined procedures. A single operation, CABG on a beating heart or repair of AAA, were performed in 27 or 19 patients. There were no significant differences with regard to intraoperative blood loss, transfusion and postoperative intubation time among the three groups. There was no operative mortality for any of the three groups. All cases were discharged without severe complications and with patent coronary bypass grafts. There was a decrease in mean total hospital costs for the combined operation group compared with the CABG group plus AAA repair group (3.34 million versus 5.87 million yen). Combined CABG on a beating heart and AAA repair on a one-step approach appears to be a safe and useful therapeutic strategy for AAA patients with CAD.

Infarction exclusion technique with transmural sutures for postinfarction ventricular septal rupture.

We present a case of postinfarction ventricular septal rupture (VSR) who underwent successful repair using a modified infarction exclusion technique. In our procedure a heterologous pericardial patch is sutured to healthy endocardium in the free wall and septum all around the infarcted area. Interrupted circular mattress sutures were placed through the ventricular wall in such a way as to exclude the VSR and the infarcted muscle of the left ventricle. We describe herein a novel procedure for repairing postinfarction VSR, by the transmural infarction exclusion technique.

Evaluation of lung injury after three-dimensional conformal stereotactic radiation therapy for solitary lung tumors: CT appearance.

PURPOSE: To evaluate the computed tomographic (CT) appearance of tumors and lung injury in patients who have undergone stereotactic radiation therapy (SRT) for solitary lung tumors. MATERIALS AND METHODS: Twenty-seven patients with primary lung cancer and four with metastatic lung cancer who underwent SRT for solitary lung tumors were enrolled for evaluation. SRT was delivered by using a three-dimensional conformal technique with a stereotactic body frame. A total dose of 48 Gy was administered in four fractions during a period of 2 weeks. After SRT, follow-up CT images were obtained every 2-3 months. Radiation-induced pulmonary injuries were classified into four patterns on CT images. The minimal lung dose to areas demonstrating pulmonary injury at CT was evaluated, and the correlation between the dose and the percentage volume of the whole lung irradiated by more than 20 Gy in total (V20) was assessed by using Spearman rank correlation. RESULTS: Tumor shrinkage continued for 2-15 months after SRT. Asymptomatic changes in the irradiated lung were noted at CT in all patients within 2-6 months (median, 4 months) after SRT. As the pattern at pulmonary CT changed, patchy consolidation was more predominantly seen as an acute change than were slight homogeneous increase in opacity, discrete consolidation, or solid consolidation; solid consolidation was the more predominantly seen late change. The minimal lung dose to the area demonstrating pulmonary injury in each patient ranged between 16 and 36 Gy (median, 24 Gy). The dose was significantly (P <.001) inversely correlated with the V20 in each patient. CONCLUSION: The reaction to SRT of the lungs seems similar to the reaction to conventional radiation therapy.

18F-FDG and 11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy.

This study was performed to investigate the feasibility of FDG- and L-[methyl-11C]methionine (Met)-PET for the follow up of lung cancer after stereotactic radiotherapy (SRT). Nine patients (pt) with solitary lung cancer underwent SRT. Met- and FDG-PET studies were performed one week before SRT and from one week to 8 months after SRT. Responses to SRT were complete in 2 pt and partial in 7 pt. Met- and FDG-PET scan showed high tracer uptake in all tumors before SRT. After SRT, standardized uptake values (SUV) of FDG and Met changed concordantly. Both decreased with time in 5 pt but did not decrease steadily in 4 pt, where 2 pt showed an increase at 1 to 2 weeks after SRT and 2 pt showed an increase at more than 3 months after SRT. The former appears to reflect the acute reaction to SRT and the latter radiation-induced pneumonitis. Although the addition of Met-PET did not provide additional information over FDG-PET, FDG- and Met-PET could be used to evaluate the treatment effect of SRT.

Clinical evaluation of dynamic arc conformal radiotherapy for paraaortic lymph node metastasis.

PURPOSE: This study was performed to evaluate the efficacy and safety of dynamic arc conformal radiotherapy, a simple intensity modulated radiation therapy (IMRT), for the treatment of paraaortic lymph node metastases. MATERIALS AND METHODS: Twenty-nine patients with paraaortic lymph node metastases were enrolled in this study. The total planned dose was 55-60 Gy. A computed tomography (CT) simulator was used in the treatment planning. RESULTS: The total radiation dose delivered was 50-63.4 Gy (median 60 Gy). Sixteen of 29 patients showed local tumor shrinkage on CT, and the 2 year in-field recurrence free survival rate was 58%. Acute Grade 1 and Grade 2 gastrointestinal disorders occurred in 31% and 17%, respectively, and acute Grade 2 liver dysfunction occurred in 7%. As a late complication, Grade 1 and Grade 2 liver dysfunction occurred in six patients (21%) and five patients (17%), respectively. There was no renal dysfunction or myelopathy detected. CONCLUSION: Dynamic arc conformal radiotherapy, a simple IMRT, is a safe and effective treatment method for paraaortic lymph node metastasis.

Cap polyposis cured by Helicobacter pylori eradication therapy.

The pathogenesis of cap polyposis remains unknown. Here, we report a patient with cap polyposis that developed simultaneously in the colon and stomach, and which regressed after Helicobacter pylori eradication. A 63-year-old man was diagnosed as having cap polyposis with mucoid stool, diarrhea, and bleeding on defecation. Following 5 weeks of total parenteral nutrition, his symptoms and hypoproteinemia improved and he was discharged, although follow-up colonoscopic findings revealed no improvement. Subsequent gastroscopy revealed diffusely erosive polyps with cap-like "fur" from the angle to the antrum of the stomach, similar to the lesions observed in the colon. Because H. pylori infection was demonstrated in the stomach, eradication therapy was administered. After this treatment, his symptoms immediately disappeared, and the polypoid lesions in the colon and stomach had completely disappeared 8 months later. Because there have been no previous reports of a relationship between H. pylori and cap polyposis, this case is of great interest.

Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame.

PURPOSE: This study was performed to evaluate the clinical outcomes of three-dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame. MATERIALS AND METHODS: Forty patients who were treated between July 1998 and November 2000 and were followed for >10 months were included in this study. Of the 40 patients, 31 had primary lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary sites of metastatic lung cancer were the colon in 4, tongue in 2, and osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment planning was performed to maintain the target dose homogeneity within 15% and to decrease the irradiated lung volume from >20 Gy to <25%. All patients were irradiated using a stereotactic body frame and received 4 times 10-12 Gy single high-dose radiation at the isocenter during a period of 5-13 days (median 12). RESULTS: The initial 3 patients received 40, and the remaining 37 patients received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6 tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%) decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%) showed a local response. During the follow-up of 4-37 months (median 19), no pulmonary complications greater than National Cancer Institute-Common Toxicity Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled during the follow-up of 6-36 months (median = 19). In 9 tumors with lung metastases that were irradiated with 48 Gy in total, 2 tumors did not show a local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at 6-12 months (median 7) after treatment during the follow-up of 3-29 months (median 18). CONCLUSION: 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful for the treatment of lung tumors.

[Three-dimensional conformal radiotherapy for extracranial tumors using a stereotactic body frame]

This paper was reviewed to evaluate the feasibility of three-dimensional (3-D) conformal radiotherapy for extracranial tumors, especially for solitary lung tumors using a stereotactic body frame. To extend the technique of stereotactic irradiation for intracranial tumors, accurate body fixation and regulation of internal target motion are essential. In our study, a stereotactic body frame was used, and daily setup accuracy was verified. As a result, its setup accuracy was maintained within 0-8.5 mm (Ave=2.5mm). In our initial clinical experiences for thirty-two patients with 6-10 non-coplanar static beams, forty or 48 Gy was irradiated. During the follow-up of 4-27 (Average=11) months, twenty-nine (94%) tumors were locally controlled without any symptomatic complications. Recently, respiratory-gated irradiation systems, CT-linac systems, a real-time tumor tracking system, Cyber-knife, and C-arm linac were developed. With all these techniques, stereotactic irradiation for extracranial tumors are future direction of three-dimensional conformal radiotherapy.