Endoscopic submucosal dissection for hypopharyngeal cancer simultaneous with immunotherapy for renal cell carcinoma.

We report a case of a man who was diagnosed with superficial hypopharyngeal cancer and recurrence of renal cell carcinoma in the duodenum, liver, and gluteus medius muscle simultaneously. He underwent endoscopic submucosal dissection for hypopharyngeal cancer in parallel with systemic immunotherapy for recurrent renal cell carcinoma, resulting in completely overcoming both malignancies. Endoscopic submucosal dissection is less invasive and can be performed in a shorter duration for treating superficial hypopharyngeal cancer compared with other treatment options, such as radiation therapy, chemotherapy, and surgery. Additionally, endoscopic submucosal carcinoma is adequately effective in controlling local lesions and has a satisfactorily good prognosis.

A novel method of Francisella infection of epithelial cells using HeLa cells expressing fc gamma receptor.

BACKGROUND: Francisella tularensis, the causative agent of tularemia, is a facultative intracellular bacterium. Although the life cycle of this bacterium inside phagocytic cells (e.g., macrophages, neutrophils) has been well analyzed, the difficulty of gene silencing and editing genes in phagocytic cells makes it difficult to analyze host factors important for the infection. On the other hand, epithelial cell lines, such as HeLa, have been established as cell lines that are easy to perform gene editing. However, the infection efficiency of Francisella into these epithelial cells is extremely low. METHODS: In order to facilitate the molecular biological analysis of Francisella infection using epithelial cells, we constructed an efficient infection model of F. tularensis subsp. novicida (F. novicida) in HeLa cells expressing mouse FcγRII (HeLa-FcγRII), and the system was applied to evaluate the role of host GLS1 on Francisella infection. RESULTS: As a result of colony forming unit count, HeLa-FcγRII cells uptake F. novicida in a serum-dependent manner and demonstrated an approximately 100-fold increase in intracellular bacterial infection compared to parental HeLa cells. Furthermore, taking advantage of the gene silencing capability of HeLa-FcγRII cells, we developed GLS1, a gene encoding glutaminase, knockdown cells using lentiviral sh RNA vector and assessed the impact of GLS1 on F. novicida infection. LDH assay revealed that GLS1-knockdown HeLa-FcγRII cells exhibited increased cytotoxicity during infection with F. novicida compared with control HeLa-FcγRII cells. Furthermore, the cell death was inhibited by the addition of ammonia, the metabolite produced through glutaminase activity. These results suggest that ammonia plays an important role in the proliferation of F. novicida. CONCLUSIONS: In this report, we proposed a new cell-based infection system for Francisella infection using HeLa-FcγRII cells and demonstrated its effectiveness. This system has the potential to accelerate cell-based infection assays, such as large-scale genetic screening, and to provide new insights into Francisella infection in epithelial cells, which has been difficult to analyze in phagocytic cells.

Role of the JAK2/STAT3 pathway on infection of Francisella novicida.

Francisella tularensis is a causative agent of the zoonotic disease tularemia, and is highly pathogenic to humans. The pathogenicity of this bacterium is largely attributed to intracellular growth in host cells. Although several bacterial factors important for the intracellular growth have been elucidated, including the type VI secretion system, the host factors involved in the intracellular growth of F. tularensis are largely unknown. To identify the host factors important for F. tularensis infection, 368 compounds were screened for the negative regulation of F. tularensis subsp. novicida (F. novicida) infection. Consequently, 56 inhibitors were isolated that decreased F. novicida infection. Among those inhibitors, we focused on cucurbitacin I, an inhibitor of the JAK2/ STAT3 pathway. Cucurbitacin I and another JAK2/STAT3 inhibitor, Stattic, decreased the intracellular bacterial number of F. novicida. However, these inhibitors failed to affect the cell attachment or the intrasaccular proliferation of F. novicida. In addition, treatment with these inhibitors destabilized actin filaments. These results suggest that the JAK2/STAT3 pathway plays an important role in internalization of F. novicida into host cells through mechanisms involving actin dynamics, such as phagocytosis.

Cancer risk by length of Barrett's esophagus in Japanese population: a nationwide multicenter retrospective cohort study.

BACKGROUND: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. METHODS: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. RESULTS: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively. CONCLUSIONS: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.

Development of a prediction score for Barrett's esophagus in Japanese health checkup settings.

BACKGROUND: The incidence of esophageal adenocarcinoma has recently increased in Asia, including Japan. A system to identify individuals at high risk for Barrett's esophagus (BE), a pre-cancerous condition of esophageal adenocarcinoma, among the general population is needed to perform endoscopic surveillance appropriately. We therefore developed risk prediction scores for BE at health checkups in Japan. METHODS: 4128 consecutive health checkup examinees were retrospectively enrolled from October 2021 to March 2022. A prediction score for BE was developed based on the linear transformation of ß-regression coefficients in a multivariable regression model incorporating BE predictors. Internal validation was performed by evaluating discrimination and calibration of the prediction model. RESULTS: Three prediction scores corresponding to BE based on its length were developed: all lengths, ≥ 1 cm, ≥ 2 cm. All scores were internally validated, and the model calibration was excellent. The performance of the prediction models was better for longer BE, with a c-statistic of 0.70 for BE ≥ 2 cm, than for shorter values. The prediction score for BE ≥ 2 cm yielded sensitivity and specificity of 52.9% and 78.6% in high-risk subjects and 91.2% and 29.3% in intermediate- or high-risk subjects, respectively. CONCLUSIONS: This prediction score can potentially increase the endoscopic detection of BE by identifying potentially high-risk individuals from the general population. This is the first report on developing a prediction score for BE that may suit the Japanese population.

Long-term outcomes of high-dose-rate brachytherapy and external beam radiotherapy without hormone therapy for high-risk localized prostate cancer.

PURPOSE: Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment. MATERIALS AND METHODS: Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined. RESULTS: Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively. CONCLUSION: HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.

Radiation­induced pleomorphic liposarcoma after hypofractionated radiotherapy following breast­conserving surgery: A case report and literature review.

Breast cancer is one of the leading causes of cancer globally. Radiotherapy following breast-conserving surgery is the standard treatment of breast cancer. Recently, hypofractionated irradiation comprising 42.56 Gy in 16 fractions was selected as a viable radiation therapeutic option. Radiation-induced sarcoma is the most prevalent secondary malignancy in patients undergoing radiotherapy after breast cancer surgery. Angiosarcomas are the predominant type of radiation-induced sarcomas, whereas liposarcomas have rarely been reported. The present report details an uncommon instance of radiation-induced pleomorphic liposarcoma that occurred 8 years after breast-conserving surgery and hypofractionated radiotherapy. The patient visited the hospital due to hardening of the tissue beneath the skin of the right breast. Ultrasonography revealed a hypoechoic mass in the lower part of the right breast containing internal blood flow. An excisional biopsy revealed that the tumor contained infiltrating spindle-shaped cells without a capsule containing pleomorphic cells. Lipoblasts were also observed and tended to differentiate into adipose tissue, leading to a diagnosis of pleomorphic liposarcoma. Immunostaining revealed negativity for cytokeratin AE1/AE3, ERG, MDM2 and S-100 protein; the Ki-67 index was ~20%. An enlargement resection involving a postoperative bed was performed because of close tumor margins. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed pale accumulation of 18F-fluorodeoxyglucose in the right chest wall, which was interpreted as a postoperative change owing to the resection biopsy. The tumor was observed in the irradiated field with no distant metastases. Following extensive resection, the patient maintained a recurrence-free survival period of 3 years and 2 months, during which no adjuvant therapy was administered. Therefore, follow-up is necessary in patients with breast cancer treated with radiotherapy.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

A Final Report on the Real Impact of the COVID-19 Pandemic on the Diagnosis of Gastrointestinal Cancer in Akita Prefecture, Japan in 2022.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the disruption of gastrointestinal cancer diagnoses remains unclear. This study investigated the actual impact on esophagogastric cancer (EGC) and colorectal cancer (CRC) diagnoses up to the third year of the pandemic in Akita Prefecture, Japan, using population-based registry data. We collected data on the annual number of EGC and CRC diagnoses using a database from the collaborative Akita Prefecture hospital-based registration. The net number of cancers diagnosed in the first three years of the pandemic (2020-2022) were compared with those diagnosed in the three years before the pandemic (2017-2019). Changes in the proportion of cancer stage and initial treatment for diagnosed EGC and CRC after the pandemic were then compared. The total number of EGCs was 9.3% lower in the first three years of the pandemic than in the three years before, probably due to its long-term declining trend. The total number of CRCs in the first three years of the pandemic exceeded that in the three years before, suggesting successful recovery of the diagnostic procedure. The proportion of cancer stages and initial treatment for EGCs and CRCs remained largely unchanged after the onset of the pandemic. Based on the population-based registry data from the first three years of the pandemic, the disruption of gastrointestinal cancer diagnoses caused by the pandemic is settling down without any substantial disease progression, even in Akita Prefecture, the area with the highest incidence of cancer in all of Japan.

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Disproportionate cancer worries in ultra-short-segment Barrett's esophagus in Japan.

Objectives: Although Barrett's esophagus (BE), especially ultra-short-segment BE (USSBE), is very frequently diagnosed in Japan, how subjects feel about receiving a diagnosis of BE is unclear. We therefore prospectively investigated cancer worry in subjects who received a BE diagnosis. Methods: Self-administered questionnaires were sent to subjects who were diagnosed with BE at three health checkup institutes in Akita Prefecture, Japan. The cancer worry scale (CWS) was used to quantitatively assess the fear of developing cancer. The BE subjects were classified into USSBE <1 cm and non-USSBE ≥1 cm groups. Factors associated with the CWS were investigated using logistic regression analyses. Results: A total of 325 (31%) subjects, comprising 229 USSBE and 96 non-USSBE patients were included in this study. Compared with the USSBE group, the non-USSBE group had a significantly higher frequency of a history of a BE diagnosis and perception of carcinogenesis. However, the CWS was similar between the USSBE and non-USSBE groups, with a median CWS of 12.5 (3.75) versus 12.7 (3.65). A multivariate logistic regression analysis revealed that while positive reflux symptoms were significantly associated with a positive CWS, the BE length was not significantly associated with it, with an odds ratio (95% confidence interval) of 1.3 (0.75-2.2). Conclusions: A BE diagnosis promotes a similar level of worry about cancer among subjects, irrespective of the length of BE. In Japan, since USSBE poses a much lower cancer risk than non-USSBE, the former may frequently be associated with a disproportionate cancer worry relative to the latter. (UMIN000044010).

Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. METHODS: The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. RESULTS: The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness ≥1000 µm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R = .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. CONCLUSIONS: Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.

[A case of severe inflammatory bowel disease triggered by vaccination with SARS-CoV-2 mRNA].

A 64-year-old woman received a third dose of SARS-CoV-2 mRNA vaccine. On the next day, she developed fever, diarrhea, and abdominal pain and had bloody stools. Total colonoscopy revealed deep ulceration on the whole colon. She was treated with corticosteroid and infliximab and her symptoms improved. She was diagnosed with severe enteritis resembling ulcerative colitis triggered by SARS-CoV-2 mRNA vaccination.

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

A Follow-up Report on the Diagnosis of Gastrointestinal Cancer during the COVID-19 Pandemic in Akita Prefecture, Japan in 2021.

We recently reported the decrease in the number of gastrointestinal (GI) cancer diagnoses in 2020 due to disturbance of the healthcare system by the coronavirus disease 2019 (COVID-19) pandemic, using a hospital-based cancer registration system in Akita prefecture, Japan. In this study, we extended the research by showing the latest data (2021) on the number of cancers and examinations. Information on the occurrence and stage of esophageal, gastric, and colorectal cancers was collected from the same database. The number of GI examinations (cancer screening procedures and endoscopic examinations) was also investigated. Following the immediate decrease in the numbers of both GI examinations and GI cancer diagnoses in 2020, a rebound increase in the numbers of GI cancer diagnoses-especially colorectal cancers-was observed in 2021, resulting from an increased number of GI examinations i.e., the total number of colorectal cancers in 2021 increased by 9.0% and 6.8% in comparison to 2020 and pre-pandemic era, respectively. However, the rebound increase in 2021 was largely due to an increase in early-stage cancers, and there was no apparent trend toward the increased predominance of more advanced cancers. It therefore seems that we managed to escape from the worst-case scenario of disturbance of the healthcare system due to pandemic (i.e., an increase in the number of more advanced cancers due to delayed diagnoses). We need to continue to watch the trends in Akita prefecture, which has the highest rate of mortality from the 3 major GI cancers in Japan.

RNA-binding protein LIN28A upregulates transcription factor HIF1α by posttranscriptional regulation via direct binding to UGAU motifs.

Hypoxia-inducible factor 1α (HIF1α) is a transcription factor that regulates angiogenesis under hypoxic conditions. To investigate the posttranscriptional regulatory mechanism of HIF1α, we performed a cell-based screening to reveal potential cis-elements and the regulatory RNA-binding proteins that act as trans-factors. We found that LIN28A promoted HIF1α protein expression independently of the downregulation of microRNA let-7, which is also directly mediated by LIN28A. Transcriptome analysis and evaluation of RNA stability using RNA-seq and SLAM-seq analyses, respectively, revealed that LIN28A upregulates HIF1A expression via mRNA stabilization. To investigate the physical association of LIN28A with HIF1A mRNA, we performed enhanced crosslinking immunoprecipitation in 293FT cells and integrally analyzed the transcriptome. We observed that LIN28A associates with HIF1A mRNA via its cis-element motif "UGAU". The "UGAU" motifs are recognized by the cold shock domain of LIN28A, and the introduction of a loss-of-function mutation to the cold shock domain diminished the upregulatory activities performed by LIN28A. Finally, the microvessel density assay showed that the expression of LIN28A promoted angiogenesis in vivo. In conclusion, our study elucidated the role of LIN28A in enhancing the HIF1α axis at the posttranscription layer.

Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.