Search

The aim of this article is to review unrecognized toxicities resulting from radiation therapy of digestive neoplasms. Due to their precocious occurrence, acute toxicities are well-known by radiation oncologist, and their treatment well-established. Thus, acute toxicities will not be described in this review. We will focus on incidence, diagnosis, and management of late and uncommon toxicities occurring in the digestive tract and digestive organs. Prevention, by respecting healthy tissues constraints, is the main tool to reduce incidence of those rare complications. Nonetheless, once installed, late toxicities remain a major burden in terms of quality of life and can even be life threatening. Hence, information and education about their diagnosis and management is important., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Aims: The duodenum is a critical organ at risk while planning radiation for gastrointestinal cancers or para-aortic nodes from gynaecological cancers due to the close proximity to the target volumes. The aim of this study was to assess the dosimetric parameters of the duodenum received during radiotherapy to upper gastrointestinal and gynaecological malignancies and their correlation with clinical toxicity., Materials and Methods: All adult patients who were treated with radiotherapy for primary upper gastrointestinal cancers (liver, stomach, pancreas, gall bladder) and patients with gynaecological cancers who were treated with extended fields in view of para-aortic nodal involvement from 1 January 2010 to 31 July 2015 were considered for the study. The radiation dose prescription was 45 Gy to the elective clinical target volume and 52.5-60 Gy to the gross nodal volume. The planning computed tomography scan was retrieved and the dose-volume histogram parameters for the duodenum were extracted. The relative volumes of duodenum receiving a dose from 40 to 55 Gy in increments of 5 Gy (V40Gy, V45Gy, V50Gy, V55Gy) were also noted., Results: Of the 258 patients assessed, 30 patients (12.1%) were detected to have grade 2-4 toxicities related to the duodenum as detected on endoscopy. Most had grade 3 toxicity - 18 patients were diagnosed with grade 3 toxicity and four patients had grade 4 toxicity. The most common toxicity noted was duodenal ulceration seen in 16 patients. The other toxicities were duodenal stricture in eight patients, duodenal perforation in five patients and one patient was reported to have duodenal fistula. The patients with duodenum receiving V55Gy ≥ 1 cm 3 (7.7% versus 3.8%, P = 0.014) and V50Gy ≥ 4 cm 3 (7.7% versus 3.8%, P = 0.014) had higher grade ≥2 duodenal toxicity., Conclusion: A threshold level of V55Gy ≥ 1 cm 3 and V50Gy ≥ 4 cm 3 for the duodenum is predictive of clinically significant grade 2 and higher toxicity and could serve as valid dose constraints for the duodenum., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To test feasibility and safety of hypofractionated intensity modulated radiotherapy (H-IMRT) in pancreatic adenocarcinoma (PAC) treatment., Methods: Patients with unresectable nonmetastatic PAC were prospectively enrolled on a pilot study. Patients received H-IMRT to gross tumor volume to a total dose of 52 Gy (4 Gy/fraction). Toxicity rates, duodenal dosimetric parameters, and clinical outcomes were evaluated., Results: Ten patients received H-IMRT regimen. Objective tumor response was recorded in all patients but one. Gastrointestinal toxicity was the most common acute side effect and its severity moderately correlated with duodenal maximum dose (ρ = 0.46) and percentage of duodenal volume exposed to 5 Gy (ρ = 0.46). The 1-year overall and disease-free survival were 83.3% and 68.6%, respectively., Conclusion: H-IMRT seems to guarantee a high local control rate without severe toxicity. Its use in unresectable nonmetastatic PAC needs to be further investigated., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: We previously have shown the feasibility of duodenum sparing using a biodegradable hydrogel spacer in pancreatic cancer radiation therapy. In this study, we propose an overlap volume histogram (OVH) prediction model to select patients who might benefit from hydrogel placement and to predict the hydrogel spacing required to achieve clinical constraints., Methods and Materials: OVH metrics for the duodenum were collected from the stereotactic body radiation therapy plans of 232 patients with unresectable pancreatic cancer (33 Gy in 5 fractions). OVH metrics L 9cc and L 3cc were defined as the tumor volume expansion distance at which 9 cm 3 and 3 cm 3 volumes of the duodenum overlap with tumor. D 9cc and D 3cc of the duodenum were defined as the dose-volume histogram dose to 9 cm 3 and 3 cm 3 , respectively, of the duodenum. Prediction models were established by linear regression between L x and D x , where x = 3 cm 3 and 9 cm 3 . OVH thresholds were obtained for predicting the target spacer thickness. The accuracy of the prediction model was then evaluated using treatment plans on pre-and post-hydrogel injection computed tomography scans from 2 cadaver specimens and 6 patients with previously treated locally advanced pancreatic cancer with simulated spacer., Results: Linear regression analysis showed a significant correlation between L x and D x (r 2  = 0.51 and 0.51 for L 3cc -D 3cc and L 9cc -D 9cc , respectively; both P < .01). The OVH thresholds were Lˆ 3cc  = 7 mm and Lˆ 9cc  = 13 mm. The observed planning doses D 3cc and D 9cc of duodenum from pre-and post-hydrogel injection computed tomography scans of cadaver specimens and clinical patients with simulated spacer using predicted target spacer thickness were within the OVH model prediction range., Conclusion: Our model may predict which patients require placement of a hydrogel spacer before stereotactic body radiation therapy to meet predefined dose constraints. Furthermore, by predicting the required target hydrogel thickness, the spacer injection can be better guided to improve efficacy., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data., Material and Methods: A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials., Results: Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n=0.070, m=0.46, TD 50(1) [Gy]=183.8, while the values for the model incorporating the individual patient data were n=0.193, m=0.51, TD 50(1) [Gy]=299.1., Conclusions: LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims and Background: This study was designed to evaluate the prevalence of gastroduodenal complications and factors that contribute to the development of symptomatic GD toxicity in cirrhotic patients with perihilar hepatocellular carcinoma (HCC), after an acceptable dose of radiotherapy., Methods: This was a retrospective study of 40 cirrhotic patients with perihilar HCC treated with radiotherapy from August 2008 to September 2010. Esophagogastroduodenoscopy was performed before and after radiotherapy. The maximum point dose to the gastroduodenum was 35.8 to 44 Gy (2 Gy equivalent, α/β = 10). Gastroduodenal complications were graded using the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). Child-Pugh score was assessed 3 months after completion of radiotherapy, and compared with the score obtained before radiotherapy., Results: Gastroduodenal complications were observed in 22 patients (55.0%) after radiotherapy. Twelve of these patients (30%) needed medical interventions. Although there were no significant factors that directly correlated with the prevalence of all-grade gastroduodenal complications, symptomatic complications (grade 2 or higher) were significantly related to the degree of Child-Pugh score elevation after radiotherapy (P = 0.002)., Conclusions: Considerable gastroduodenal complications developed in cirrhotic patients with perihilar HCC after an acceptable dose of radiotherapy. The aspects of gastroduodenal toxicities and the maintenance of liver function after radiotherapy may be an important issue in patients who undergo this treatment.

Purpose: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity., Methods and Materials: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scored according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity., Results: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm(3) were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity., Conclusions: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm(3) may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints, consideration should be given to other treatment approaches such as resection or initial chemotherapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT)., Patients and Methods: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated., Results: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors., Conclusion: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities., Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity., Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity., Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC., Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods., Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm(3)) receiving a dose of at least 55 Gy (V(55 Gy) > 1 cm(3)), and a maximum point dose >60 Gy. Of these factors, only V(55 Gy) ≥1 cm(3) was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002)., Conclusions: This study demonstrates that a duodenal V(55 Gy) >1 cm(3) is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a dosimetric constraint when treating patients with unresectable pancreatic cancer with concurrent chemoradiation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT)., Methods and Materials: From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meier and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity., Results: Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V(20Gy) to V(35Gy) of duodenum were significantly associated with GI toxicity (all p ≤ 0.05). On MVA, the V(25Gy) of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V(25Gy) of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V(25Gy) ≤ 45% and V(25Gy) > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V(35Gy) is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V(35Gy) ≤ 20% and V(35Gy) > 20%, respectively (p = 0.04)., Conclusions: DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI toxicity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy., Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0., Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p=0.043). There were no radiation-related deaths., Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT., Methods and Materials: Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25 Gy in a single fraction. Dose-volume histogram (DVH) endpoints evaluated include V(5) (volume of duodenum that received 5 Gy), V(10), V(15), V(20), V(25), and D(max) (maximum dose to 1 cm(3)). Normal tissue complication probability (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models., Results: The median time to Grade 2-4 duodenal toxicity was 6.3 months (range, 1.6-11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V(10)-V(25) and D(max) all correlated significantly with duodenal toxicity (p<0.05). In particular, V(15)≥9.1 cm(3) and V(15)<9.1 cm(3) yielded duodenal toxicity rates of 52% and 11%, respectively (p=0.002); V(20)≥3.3 cm(3) and V(20)<3.3 cm(3) gave toxicity rates of 52% and 11%, respectively (p=0.002); and D(max)≥23 Gy and D(max)<23 Gy gave toxicity rates of 49% and 12%, respectively (p=0.004). Lyman NTCP model optimization generated the coefficients m=0.23, n=0.12, and TD(50)=24.6 Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p=0.001)., Conclusions: Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Cancer of unknown primary (CUP) is defined as histologically confirmed metastases in the absence of an identifiable primary tumor. Patients with solely liver metastases from adenocarinomas represent the most frequent subgroup with an unfavourable prognosis. The medium survival averages 6 to 9 months. No chemotherapheutic standard has been established., Case: We present a patient with hepatic CUP. After cycles of chemotherapy and hemihepatectomy the tumor returned and showed hepatic progression. The patient was evaluated for selective internal radiation therapy (SIRT). Three years after diagnosis she is still alive and tumorfree. Despite a good result and disease control our patient suffered radiation-induced ulceration in the oesophagus, stomach, and duodenum. This side effect appears in up to 12 % of patients, often very late after treatment, is refractory to pharmacotherapy and persistent over a long time., Conclusions: SIRT is a new, effective treatment in patients with hepatic CUP. Because of the anticipated increase of this therapy, adverse side effects such as ulcerations in the upper-GI tract secondary to ectopic implantation of microspheres may be seen more commonly. Awareness of this and the recognition of microspheres in biopsies is cardinal for appropriate management and maintenance of the patient's quality of life.

Purpose: To evaluate three-dimensional conformal (3D-CRT), intensity-modulated (IMRT) and respiration-gated radiotherapy (RGRT) techniques for gastric irradiation for target coverage and minimization of renal doses. All techniques were four-dimensional (4D)-CT based, incorporating the intrafractional mobility of the target volume and organs at risk (OAR)., Methods and Materials: The stomach, duodenal C-loop, and OAR (kidneys, liver, and heart) were contoured in all 10 phases of planning 4D-CT scans for five patients who underwent abdominal radiotherapy. Planning target volumes (PTVs) encompassing all positions of the stomach (PTV(all phases)) were generated. Three respiratory phases for RGRT in inspiration and expiration were identified, and corresponding PTV(inspiration) and PTV(expiration) and OAR volumes were created. Landmark-based fields recommended for the Radiation Therapy Oncology Group (RTOG) 99-04 study protocol were simulated to assess PTV coverage. IMRT and 3D-CRT planning with and without additional RGRT planning were performed for all PTVs, and corresponding dose volume histograms were analyzed., Results: Use of landmark-based fields did not result in full geometric coverage of the PTV(all phases) in any patient. IMRT significantly reduced mean renal doses compared with 3D-CRT (15.0 Gy +/- 0.9 Gy vs. 20.1 Gy +/- 9.3 Gy and 16.6 Gy +/- 1.5 Gy vs. 32.6 Gy +/- 7.1 Gy for the left and right kidneys, respectively; p = 0.04). No significant increase in renal sparing was seen when adding RGRT to either 3D-CRT or IMRT. Tolerance doses to the other OAR were not exceeded., Conclusions: Individualized field margins are essential for gastric irradiation. IMRT plans significantly reduce renal doses, but the benefits of RGRT in gastric irradiation appear to be limited.

Non-traumatic duodenocaval fistulae are rare, but may be the source of massive gastrointestional bleeding with associated fever and sepsis. These fistulae result from penetrating duodenal peptic ulcers or right nephrectomy and subsequent radiation to the upper abdomen. The outcome depends on early diagnosis and surgery before a potentially fatal hemorrhage occurs. The therapy of choice includes closure of the fistula and repair of the duodenum and inferior vena cava. We describe the seventh case with radiogenic duodenal ulcer. Gastrointestinal bleeding occurred 10 years after radical nephrectomy and radiation (60 Gy). The patient survived following partial pancreatoduodenectomy (Whipple).

Clinical features were studied of the esophago gastroduodenal zone lesions in 136 patients with chronic glomerulonephritis. The occurrence of the above lesions was found out to appreciably affect the clinical symptomatology and the course of the underlying disease in those persons who have come to be exposed to ionizing radiation. It is necessary that pathogenetic factors be taken into consideration, such as internal irradiation, bodily intoxication with nitrogenous constituents, disturbed microcirculation and motor-and-evacuatory function of the alimentary canal in order that we might prognosticate the course of the disease and choose the relevant mode of treatment.

On the basis of a case of life-threatening haemorrhage from a postbulbar duodenal ulcer two and a half year after radiotherapy carried out on a non-Hodgkin-lymphoma, cases of the genesis and the diagnostics of this late complication are discussed.

Acute duodenal ulcers are produced in mice as a remote ("abscopal") effect of irradiation to the lower mediastinum. Such lesions have been examined with scanning electron microscopy at 5, 8 and 28 days after irradiation with 18 Gy of X-rays. All the ulcers occur within the first 1 cm long segment of the duodenum which is endowed with Brunner's glands. The single lesions vary in size, shape and position. The damaged area often includes much of the duodenal circumference and is distinguished by conical or rudimentary villi, or even by the complete absence of villi. In contrast, around the periphery of the ulcer the villi are mostly vertical. Although the floor of these lesions appears to be covered with a continuous epithelial layer, during the first 4 weeks after irradiation the severity of the focal duodenal damage seems to increase gradually with time. The lesions have been compared with specimens from unirradiated mice and also with samples taken 3 days after partial thoracic irradiation when little damage is seen. The pattern of fully developed duodenal lesions differs greatly from that seen after direct irradiation where damage has not included localised ulceration in the samples of jejunum so far examined. The lesions induced by partial thoracic irradiation may be related to radiation injury to vascular or autonomic nerve targets in the lower mediastinum. Such injury could result in malfunction of the pyloric sphincter or could alter the secretion by Brunner's glands and thus lead to duodenal ulceration.