Search

Background: This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC). Methods: Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20-74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy [RBE] per fraction). Results: All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years. Conclusion: Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.

Background This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC). Methods Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20–74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy [RBE] per fraction). Results All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years. Conclusion Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.

There are no clinical reports of long‐term follow‐up after carbon‐ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6 Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n = 45] and scanning [n = 211]), and who were followed for more than 1 year, were analyzed. The biochemical relapse‐free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan‐Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow‐up of 7.0 (range 1.1‐10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5‐year bRF rates of the low‐, intermediate‐, and high‐risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5‐year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long‐term follow‐up results showed that a CIRT regimen of 51.6 Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique., A 51.6 Gy (relative biological effectiveness) carbon‐ion radiotherapy regimen in 12 fractions for localized prostate cancer with long‐term follow‐up yielded a good therapeutic outcome and low toxicity rates in both passive and scanning beam irradiation without significant difference.

There are no clinical reports of long-term follow-up after carbon-ion radiotherapy (CIRT) using a dose of 51.6Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n=45] and scanning [n=211]), and who were followed for more than 1year, were analyzed. The biochemical relapse-free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan-Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow-up of 7.0 (range 1.1-10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5-year bRF rates of the low-, intermediate-, and high-risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5-year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long-term follow-up results showed that a CIRT regimen of 51.6Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique.

Highlights • Carbon-ion re-irradiation for pancreatic cancer; feasibility and efficacy. • Adjuvant chemotherapy improve local control of re-irradiation using carbon ions. • Carbon-ion radiotherapy for recurrent pancreatic cancer; reasonable option., Background and purpose Patients who receive carbon-ion radiotherapy (C-ion RT) for primary pancreatic cancer may experience locoregional recurrence; however, the treatment options for such patients are limited. We aimed to investigate the feasibility and efficacy of carbon-ion re-irradiation for patients with pancreatic cancer who experienced recurrence after initial C-ion RT. Materials and methods Twenty-one patients with recurrent pancreatic cancer who underwent repeat C-ion RT between December 2010 and November 2016 at our institute were retrospectively evaluated. The sites of post-initial C-ion RT failure were in-field central in 16 patients (76.2%) and marginal in 5 (23.8%). The median doses of initial and repeat C-ion RT were both 52.8 Gy (relative biological effectiveness [RBE]). Thirteen patients (61.9%) received concurrent chemotherapy with re-irradiation, while 11 (52.4%) received adjuvant chemotherapy. Results The median follow-up period after re-irradiation was 11 months. The 1-year local control, progression-free survival, and overall survival rates were 53.5%, 24.5%, and 48.7%, respectively. Toxicity data was obtained from the patients’ charts. Only 1 patient (4.8%) developed grade 3 acute toxicities and none developed grade ≥3 late toxicities. Univariate analysis indicated that patients who received adjuvant chemotherapy had significantly improved local control rates compared with those who did not; the 1-year local control rates were 80.0% and 0.0%, respectively (P = 0.0469). Conclusion Repeating C-ion RT may be a reasonable option with tolerable toxicity for patients with recurrent pancreatic cancers. Adjuvant chemotherapy appears to improve the local control rate. This is the first study to examine re-irradiation using C-ion for recurrent pancreatic cancer after initial C-ion RT.

Highlights • High LET and high RBE of carbon ion made it a promising tool for treating pancreatic cancers. • Dose averaged LET minimum within the GTV is significantly associated with local control. • Outcome of CIRT in pancreatic cancers can be improved by modulating dose averaged LET within the GTV., Background and purpose High linear energy transfer (LET) radiation carbon-ion radiotherapy (C-ion RT) is one of the most promising modalities for treating unresectable primary pancreatic cancers. However, how LET contributes to a therapeutic effect is not clear. To assess whether there is an enhanced effect of high LET radiation on tumour control, we aimed to determine the impact of dose-averaged LET on local control (LC) of primary pancreatic tumours. Materials and methods A retrospective analysis of 18 patients with primary pancreatic carcinomas treated with definitive C-ion RT with concurrent chemotherapy in 2013 was conducted. The dose of irradiation was 55.2 Gy (RBE). The relationship between dose-averaged LET and LC of primary tumours was evaluated. Results All patients had histologically confirmed adenocarcinoma. The median follow-up duration was 22 months. The actuarial LC and overall survival (OS) at 18 months were 62.5% and 70.1%, respectively. There were no cases of grade ≥3 late toxicities observed. Local recurrences developed in four patients (22%), all of which were infield central recurrences. Although there were no significant differences in gross tumour volume (GTV) dose coverage, patients with higher minimum dose-averaged LET (LETmin) values within the GTV had better LC (dose-averaged LETmin ≥44 keV/microm; 18-months LC 100.0% vs 34.3%; p = 0.0366). Conclusion Dose-averaged LETmin within the GTV was significantly associated with LC of primary pancreatic cancers. Our data suggest that outcomes for patients with unresectable primary pancreatic cancers receiving C-ion RT can be improved by modulating the dose-averaged LET within the GTV.

Background and purpose High linear energy transfer (LET) radiation carbon-ion radiotherapy (C-ion RT) is one of the most promising modalities for treating unresectable primary pancreatic cancers. However, how LET contributes to a therapeutic effect is not clear. To assess whether there is an enhanced effect of high LET radiation on tumour control, we aimed to determine the impact of dose-averaged LET on local control (LC) of primary pancreatic tumours. Materials and methods A retrospective analysis of 18 patients with primary pancreatic carcinomas treated with definitive C-ion RT with concurrent chemotherapy in 2013 was conducted. The dose of irradiation was 55.2 Gy (RBE). The relationship between dose-averaged LET and LC of primary tumours was evaluated. Results All patients had histologically confirmed adenocarcinoma. The median follow-up duration was 22 months. The actuarial LC and overall survival (OS) at 18 months were 62.5% and 70.1%, respectively. There were no cases of grade ≥3 late toxicities observed. Local recurrences developed in four patients (22%), all of which were infield central recurrences. Although there were no significant differences in gross tumour volume (GTV) dose coverage, patients with higher minimum dose-averaged LET (LETmin) values within the GTV had better LC (dose-averaged LETmin ≥44 keV/microm; 18-months LC 100.0% vs 34.3%; p = 0.0366). Conclusion Dose-averaged LETmin within the GTV was significantly associated with LC of primary pancreatic cancers. Our data suggest that outcomes for patients with unresectable primary pancreatic cancers receiving C-ion RT can be improved by modulating the dose-averaged LET within the GTV.

There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose–volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed. Treatment was planned using Xio-N. The median follow-up duration was 53 months, and the median clinical target volume was 32.3 mL. Three patients developed grade 2 RP, and one patient developed grade 3 interstitial pneumonitis. None of the patients developed grade 4 or 5 RP. The dose-volume parameters of the normal lung irradiated at least with 5–30 Gy (RBE), and the mean lung dose was significantly lower in patients with grade 0–1 RP than in those with grade 2–3 RP. Pretreatment with higher SP-D and interstitial pneumonitis were significant factors for the occurrence of symptomatic RP. The present study showed a certain standard for single-fraction carbon-ion radiotherapy that does not increase the risk of RP, however, further validation studies are needed.

Purpose We investigated the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally recurrent rectal cancer (LRRC). Patients and methods Data from patients with LRRC treated with C-ion RT from November 2003 to December 2014 at three institutions were retrospectively analyzed. The endpoints of this clinical trial were overall survival (OS), local control (LC), and acute/late toxicity. Results A total of 224 patients' data were collected. The prescribed dose was 70.4 Gy (relative biological effectiveness [RBE]-weighted absorbed dose) or 73.6 Gy (RBE) in 16 fractions. The median follow-up period from the initiation of C-ion RT was 62 months (range 6–169 months). The OS rates were 73% (95% confidence interval [CI], 67%–79%) at 3 years and 51% (95%CI 44%–58%) at 5 years. The LC rates were 93% (95%CI 88%–96%) at 3 years, and 88% (95%CI 82%–93%) at 5 years. Grade 3 acute toxicity was observed in three patients: gastrointestinal toxicity (n = 1) and pelvic infection (n = 2). Grade 3 late toxicity was observed in 12 patients: skin reaction (n = 2), gastrointestinal toxicity (n = 2), neuropathy (n = 1), and pelvic infection (n = 7). There was no grade 4 or 5 acute or late toxicity. Conclusions This first multi-institutional analysis of C-ion RT for LRRC indicated relatively favorable outcomes with limited toxicities.

Purpose/Objective(s) 70% of patients able to receive surgical resection for pancreatic adenocarcinoma may ultimately experience recurrence; 25-35% have disease in the remnant pancreas or tumor bed. Surgical re-resection carries notable risks for morbidity, while success with photon irradiation has been limited. Carbon-ion radiotherapy (CIRT) has demonstrated unique promise in the treatment of locally advanced pancreatic cancer (LAPC). An initial cohort from 2011-2015 was published in 2017; here, we provide an update on CIRT safety and efficacy for post-surgical salvage of locally recurrent pancreatic cancer, with 60 cases from 2007 to 2020. Materials/Methods Patients with locoregional recurrence following resection of pancreatic cancer were eligible. CIRT was conducted using 48.0 to 55.2 Gy (RBE) in 12 fractions, delivered over 3 weeks. Inclusion criteria included: 1) unresectable disease due to tumor invasion or patient refusal of re-resection; 2) absence of distant metastasis, 3) ECOG performance of 0 to 2. Patients with disease invading the GI tract, previous radiotherapy, or metallic stent placement were excluded. Results A total of 60 patients treated between January 2007 and 2020 were retrospectively reviewed. Median age was 65, with pancreatic head primary in 34 cases and body/tail in 26 cases. 34 cases underwent pancreaticoduodenectomy, with 26 distal pancreatectomies. 14 cases recurred in the residual pancreas, while 46 cases recurred in surrounding tissue. 16 cases received 48 – 52.8 Gy (RBE) via dose escalation, with 44 cases receiving 55.2 Gy (RBE). Grade 3 hematologic toxicity was seen in 3 cases, with no other G3+ acute or late toxicity was noted. 2-year local control was achieved in 56% for 48-52.8 Gy (RBE) and 61% for 55.2 Gy (RBE) cohorts. 2-year survival was 48% in the high dose cohort, with median survival time (MST) of 23 months. Conclusion CIRT for postoperative recurrence of pancreatic cancer compared favorably to conventional chemoradiation salvage (2-year survival 38%, 16-month MST), with acceptable toxicity. CIRT may be a viable treatment alternative when re-resection is difficult.

Long-term outcomes after surgical resection of bile duct cancer remain unsatisfactory, and survival, particularly after tumor recurrence, is poor. Gemcitabine and cisplatin combination (GC) therapy is the standard first-line treatment; however, second-line approaches are yet to be established. Radiotherapy may prolong the survival of patients with advanced biliary tract cancer, and particle radiotherapy delivers a more concentrated dose than conventional radiotherapy to deeper tumors. The present report describes the long-term survival of a 65-year-old man with distal bile duct cancer of pathological stage IIA (T2N0M0; depth of invasion, 5.5 mm) following multimodal treatment. Following subtotal stomach-preserving pancreatoduodenectomy, multiple hepatic recurrences were identified 9 months later, and GC therapy was initiated. The tumors were no longer evident 18 months later, and GC therapy was discontinued at the patient's request. A computed tomography (CT) scan performed 30 months after surgery identified a new solitary hepatic recurrence and duke pancreatic monoclonal antigen type-2 (DUPAN-2) levels were increased. Further GC therapy was declined. Carbon ion radiotherapy (CIRT) at a dose of 60 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] was then delivered in four fractions over 4 days [15 Gy (RBE)/day]. Tumor size decreased on CT, and fluorodeoxyglucose-positron emission tomography/CT revealed a decline in the standardized uptake value of the tumor after 2 months, with decreased DUPAN-2 levels. Following regrowth of the hepatic recurrence, CIRT was repeated at a dose of 66 Gy (RBE) in four fractions over 4 days [16.5 Gy (RBE)/day] and stable disease was maintained for 19 months. After 19 months, CT revealed tumor regrowth and another new metastatic lesion was identified in the left kidney. The patient received systematic chemotherapy again and died of the disease 81 months after the initial surgery. In conclusion, CIRT is a potential treatment option to control solitary recurrence of biliary tract cancer.

Carbon ion beams constitute the primary delivery method of heavy ion radiotherapy. It offers improved dose distribution, and enables concentration of dose within target volumes with minimal extraneous exposure of normal tissue, while delivering superior biological effect in comparison with photon and proton technologies. Here, we review the application of this technology to various gastrointestinal cancers.

Aim Evaluation of the therapeutic efficacy of carbon-ion radiation therapy for isolated lymph node recurrence following curative resection of esophageal cancer. Materials and methods Ten cases with lymph node recurrence after esophageal cancer surgery were treated with carbon-ion radiation therapy. A total of 48.0 Gy [relative biologic effectiveness (RBE)] was delivered over 3 weeks with a daily dose of 4.0 Gy (RBE). Results The median follow-up duration was 27.1 months (range=3-92.0 months) after carbon-ion radiation therapy. The local control rates at 2, 3 and 5 years were 92.4%. The overall survival rates at 2, 3 and 5 years were 70.0%, 58.3% and 21.9%. The median survival period was 45.3 months after carbon-ion radiation therapy. There were no toxicities of grade 3 or higher. Conclusion Carbon-ion radiation therapy may be a safe and effective treatment option for isolated lymph node recurrence after radical surgery for esophageal cancer.

The efficacy and safety of carbon ion radiotherapy (C-ion RT) for locoregional recurrence after surgery for pancreatic cancer were retrospectively evaluated. The results for 30 patients showed that C-ion RT was performed safely with relatively long overall survival, good local control, and minimal toxicity.

Purpose The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC). Methods and Materials Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2 Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated. Results In total, 72 patients were included in this study. Tumors in the head of the pancreas were seen in 30 patients (42%), while those in the body or tail of the pancreas were seen in 42 patients (58%). Fifty-six patients (78%) received concurrent chemotherapy. The OS rates were 73% (95% confidence interval [CI], 62%-84%) at 1 year, and 46% (95% CI, 31%-61%) at 2 years with a median OS of 21.5 months (95% CI, 11.8-31.2 months). The 1- and 2-year DMFS rates were 41% (95% CI, 29%-52%) and 28% (95% CI, 16%-40%), respectively. The 1- and 2-year cumulative incidences of LR were 16% (95% CI, 9%-26%) and 24% (95% CI, 14%-36%), respectively. Nineteen patients (26%) experienced acute grade 3 or 4 hematological toxicities. Two patients (3%) had grade 3 anorexia. Late gastrointestinal (GI) grade 3 toxicity was observed in 1 patient (1%). No patients developed late grade 4 or 5 toxicity. Conclusions The first multi-institutional analysis of C-ion RT for LAPC indicated relatively favorable outcomes with limited toxicities, especially for tumors not in close proximity to GI tract.

Background: The purpose of the present study was to evaluate the efficacy and safety of single-fraction carbon-ion radiotherapy (CIRT) in patients with non-small cell lung cancer. Methods: Patients with histologically confirmed non-small cell lung cancer, stage T1-2N0M0, and treated with single-fraction CIRT (50Gy (relative biological effectiveness)) between June 2011 and April 2016 were identified in our database and retrospectively analyzed. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: The study included 57 patients, 22 (38.6%) of whom had inoperable cancer. The median age was 75 years (range: 42&ndash, 94 years), and the median follow-up time was 61 months (range: 6&ndash, 97 months). The 3- and 5-year overall survival rates were 91.2% and 81.7%, respectively. All survivors were followed up for more than three years. The 3- and 5-year local control rates were 96.4% and 91.8%, respectively. No case of &ge, grade 2 pneumonitis was recorded. Conclusions: This study suggests that single-fraction CIRT for T1-2N0M0 non-small cell lung cancer patients is feasible and can be considered as one of the treatment choices, especially in medically inoperable patients.

The expression of genes can be influenced by the balance of histone acetylation and/or histone demethylation, with an imbalance of these processes possibly observed in many cancers. The histone demethylase LSD1 inhibitor activity is associated with selective transcriptional regulation and alterations in the gene expression. However, the exact mechanisms underlying the antitumor effects of LSD1 inhibitors are not fully understood. The antitumor effects of NCL1, an LSD1 inhibitor, in esophageal squamous cell cancer (ESCC) cell lines were evaluated. A comprehensive analysis of the changes in the gene expression in ESCC cell lines induced by NCL1 was carried out using a microarray analysis. A loss-of-function assay using a siRNA analysis was performed to examine the oncogenic function of the gene. NCL1 strongly inhibited the cell growth of T.Tn and TE2 ESCC cells and induced apoptosis. According to the microarray analysis, 81 genes in the T.Tn cells and 149 genes in the TE2 cells were up- or down-regulated 2-fold or more by NCL1 exposure. Among these genes, 27 were contained in both cell lines and exhibited similar expression patterns. PHLDB2, one of the genes down-regulated by NCL1, was overexpressed in the ESCC tumor tissues. Moreover, a high expression level of PHLDB2 was found to be significantly correlated with poor prognosis. The present observations of the comprehensive analysis of the gene expression levels provide insight into the mechanisms underlying the antitumor effects of LSD1 inhibitors in ESCC patients.

The aim of this study was to clarify the importance of microRNA‑375 (miR‑375) expression in patients with esophageal squamous cell carcinoma (ESCC) and to examine the in vivo antitumor effects of miR‑375 in a model of ESCC using a non‑viral delivery system. We estimated the miR‑375 and LDHB and AEG‑1/MTDH mRNA expression of the ESCC tumors from 85 patients. The correlation between the miR‑375 expression and clinicopathological features, including the prognosis, were evaluated. The presence of high miR‑375 expression was associated with lymphatic vessel invasion, while a low expression of miR‑375 significantly correlated with a poor prognosis for the 85 ESCC patients. We also found that there was a significant inverse correlation between the expression of miR‑375 and that of LDHB. Before the examination of miR‑375 in the in vivo assay, we confirmed that atelocollagen prolonged the accumulation of miRNA by using fluorescently‑labeled miRNA and an in vivo imaging system. We injected the miR‑375/atelocollagen complex or a control‑miRNA/atelocollagen complex into mice bearing TE2 and T.Tn xenografts via subcutaneous (s.c.) injections. The growth of both the TE2 and T.Tn tumors in the miR‑375 groups was significantly suppressed compared with that in the control‑miRNA groups. In addition, The LDHB mRNA expression of TE2 xenografts was significantly downregulated after miR‑375 treatment. In conclusion, it might be possible for the level of miR‑375 expression to be a utilized as a prognostic indicator for ESCC patients. The administration of miR‑375 using a non‑viral delivery might represent a powerful new treatment for ESCC.

Short gastric vessel division (SGVD) has been performed as a part of fundoplication for achalasia. However, whether or not SGVD is necessary is still unknown. Forty-six patients with achalasia who underwent a laparoscopic surgery with or without SGVD were analyzed. A questionnaire was administered to assess the postoperative improvement. Regarding improvement of dysphagia and postoperative reflux, there were no significant differences between SGVD (+) group and SGVD (−) group (P = 0.588 and P = 0.686, respectively). Nineteen patients (95%) in the SGVD (+) group and 24 (92%) in the SGVD (−) group answered that the surgery was satisfactory (P = 0.756). In the SGVD (+) group, the pre- and postsurgical body weight increase was +7.3%. In the SGVD (−) group, it was 8.2%. There was no significant difference of body weight increase between the 2 groups (P = 0.354). SGVD is not always required in laparoscopic surgery for achalasia.

Background The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. Methods CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). Results The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher. Conclusions CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

Purpose Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.

Although conventional staging laparoscopy (SL) has improved the diagnostic accuracy of peritoneal dissemination, novel technology is needed to increase the sensitivity of SL. We herein describe a new imaging method employing near-infrared (NIR) fluorescence imaging using a liposomal synthesized indocyanine green (ICG) liposomal derivative, LP-ICG-C18.LP-ICG-C18 is a NIR-photoactivating probe in which an ICG fluorophore is covalently conjugated with a phospholipid moiety. Nude mice were intraperitoneally injected with gastric cancer cells. Twelve days later, the mice were given intravenous injections of LP-ICG-C18 at a dose of 0.15 mg/kg. A NIR imaging system was used to identify the disseminated tumors. The disseminated nodules in mice were detected without any difficulties. Disseminated tumor nodules were collected from mice with or without injections of liposomal formulation and were transferred into the swine peritoneal cavity. The nodules in the swine peritoneal cavity were clearly and promptly defined by the NIR imaging system.NIR-fluorescing liposomal probes can effectively target peritoneal disseminated tumors and can be easily detected by a NIR imaging system. These results warrant future clinical trials of our imaging system and may contribute to a more precise diagnosis and therapeutic approach for gastric cancer patients.

Introduction Photodynamic therapy (PDT) is a less invasive option for cancer treatment that has evolved through recent developments in nanotechnology. We have designed and synthesized a novel liposome system that includes an indocyanine green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an optical imager to visualize blood, lymphatic, and bile flow, ICG has also been used as an optical sensitizer. In the present report, we evaluate the use of our novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an autologous murine model. Materials and Methods An excitation pulse beam (300 μJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity of the photodynamic therapy was evaluated in terms of cellular morphology changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. We tested the enhanced permeability and retention effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared fluorescence imaging system and fluorescence microscopy. We also examined the antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. Results Cell death and apoptosis were only observed in the PDT group receiving LP-ICG-C18. LP-ICG-C18 itself had no cytotoxic activity and showed good biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL staining. Conclusion These findings suggest that LP-ICG-C18 may be an effective intervening material in PDT for malignant disease.