Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Open interstitial brachytherapy for the treatment of local-regional recurrences of uterine corpus and cervix cancer after primary surgery.

Patients who develop locally recurrent uterine corpus or uterine cervix cancer after primary surgery are usually treated with radiotherapy. The optimal radiotherapeutic approach, however, has not been defined. We report the use of exploratory laparotomy, omental pedicle grafting, and intraoperative transperineal interstitial brachytherapy in the treatment of 28 such patients (10 with recurrent corpus and 18 with recurrent cervix cancer). In addition, 22 patients also received perioperative whole pelvic teletherapy while 21 also received a second closed interstitial application. Local control was achieved in 20 patients (71%), but only 10 (36%) continue to be alive without disease after a median of 44 months. Eighteen patients have died (17 of disease) a median of 13 months after open implant. Patients treated with a single implant (n = 7), with side wall involvement (n = 5), with tumors greater than 6 cm in size (n = 4), with a history of previous pelvic irradiation (n = 8), or with persistent disease after open interstitial therapy (n = 8), were not salvaged. Ten patients suffered acute morbidity which included deep venous thrombosis (n = 1), wound separation (n = 1), urinary infection (n = 2), wound infection (n = 2), pneumonia (n = 1), and fever (n = 3). Two other patients experienced chronic non-tumor-related comorbidities. These included a vesicovaginal fistula with a rectovaginal fistula in 1 patient and a small bowel obstruction with a ureteral stricture in another. A single individual suffered from both acute and chronic complications (fever, ureterointestinal fistula).(ABSTRACT TRUNCATED AT 250 WORDS

Treatment of recurrent gynecologic malignancies with iodine-125 permanent interstitial irradiation.

PurposeTo analyze the outcome of permanent 125I interstitial radiotherapy for unresectable retroperitoneal recurrences of gynecologic malignancies.Methods and materialsA retrospective review of 20 patients treated between 1979 and 1993 was performed to evaluate survival and morbidity associated with the interstitial 125I technique.ResultsNineteen tumors were located on the lateral pelvic wall and one in the para-aortic region. Eight patients, not previously irradiated, received external beam radiotherapy (EBRT) along with 125I interstitial implants placed at the time of celiotomy. Nineteen (95%) are dead of disease at 1-69 months of follow-up. The median survival was 7.7 months for patients treated with 125I alone and 25.4 months for those treated with both 125I and EBRT. One patient is alive without evidence of disease 69 months after 125I implantation. Fistulas, bowel obstructions, and fatal complications occurred only among patients previously irradiated.ConclusionsWhen used in a previously irradiated field, 125I interstitial radiotherapy has major morbidity and is unlikely to be associated with cure or long-term survival. In radiotherapy-naive patients with unresectable isolated recurrent gynecologic malignancies, 125I implants and EBRT are feasible and occasionally may contribute to long-term disease-free survival

Treatment of recurrent gynecologic malignancies with iodine-125 permanent interstitial irradiation.

PurposeTo analyze the outcome of permanent 125I interstitial radiotherapy for unresectable retroperitoneal recurrences of gynecologic malignancies.Methods and materialsA retrospective review of 20 patients treated between 1979 and 1993 was performed to evaluate survival and morbidity associated with the interstitial 125I technique.ResultsNineteen tumors were located on the lateral pelvic wall and one in the para-aortic region. Eight patients, not previously irradiated, received external beam radiotherapy (EBRT) along with 125I interstitial implants placed at the time of celiotomy. Nineteen (95%) are dead of disease at 1-69 months of follow-up. The median survival was 7.7 months for patients treated with 125I alone and 25.4 months for those treated with both 125I and EBRT. One patient is alive without evidence of disease 69 months after 125I implantation. Fistulas, bowel obstructions, and fatal complications occurred only among patients previously irradiated.ConclusionsWhen used in a previously irradiated field, 125I interstitial radiotherapy has major morbidity and is unlikely to be associated with cure or long-term survival. In radiotherapy-naive patients with unresectable isolated recurrent gynecologic malignancies, 125I implants and EBRT are feasible and occasionally may contribute to long-term disease-free survival

Interstitial brachytherapy for vaginal recurrences of endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy

Interstitial brachytherapy for vaginal recurrences of endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy

Primary invasive carcinoma of the vagina

BackgroundBecause primary carcinoma of the vagina comprises less than 2% of all gynecologic malignancies, the reported experience in the treatment of large numbers of patients is available only from a few major centers and most often encompasses a variety of differences in treatment selection and technique. The objective of this study was to assess the long term results of an interstitial iridium-192 afterloading implant technique using the Syed-Neblett dedicated vaginal plastic template.MethodsPatients who were treated from 1976 to 1997 were examined retrospectively.ResultsSeventy-one patients underwent interstitial implantation with (n = 61 patients) or without external beam radiotherapy. The median age was 59 years (range, 16-86 years). Patients were staged according to the International Federation of Gynecology and Obstetrics system and included Stage I (n = 10 patients), Perez modification Stage IIA (n = 14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15 patients), and Stage IV (n = 7 patients). Each implant delivered an approximately 20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with integrated external beam radiotherapy. Local control was achieved in 53 patients (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year, 5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%, respectively. By stage, 5-year disease free survival rates included Stage I, 100% of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III, 30% of patients; and Stage IV, 0% of patients. The factors disease stage and primary lesion size independently influenced the survival rates. Significant complications occurred in 9 patients (13%) and included necrosis (n = 4 patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1 patient).ConclusionsInterstitial irradiation can effect local control in the majority of patients with primary carcinoma of the vagina with acceptable morbidity. Long term cure is demonstrable in patients with Stage I-III disease

Long-term results of low-dose-rate interstitial-intracavitary brachytherapy in the treatment of carcinoma of the cervix.

PurposeBrachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this retrospective study (spanning a 20-year period) was to determine the outcome of interstitial low-dose-rate brachytherapy in the treatment of bulky or locally advanced cervical cancer. The long-term survival and safety of this technique were evaluated, along with its impact on local and locoregional control, disease-free survival, and complications.Methods and materialsA total of 185 previously untreated patients with cervical cancer were treated between 1977 and 1997. According to the International Federation of Gynecology and Obstetrics classification, 21 patients had Stage IB (barrel), 77 Stage II, 77 Stage III, and 10 Stage IV disease. All patients were treated by a combination of external megavoltage irradiation to the pelvis to a dose of 5040 cGy followed by interstitial-intracavitary implants to a dose of 40-50 Gy to the implanted volume in two applications.ResultsClinical local control was achieved in 152 (82%) of the 185 patients. A 5-year disease-free survival rate of 65%, 67%, 49%, and 17% was achieved for patients with Stage IB, II, III, and IV disease, respectively. Eighteen (10%) of the 185 patients developed Radiation Therapy Oncology Group Grade 3 or 4 late complications.ConclusionPatients with locally advanced cervical cancer, or with distorted anatomy, may be treated adequately with interstitial brachytherapy to achieve excellent locoregional control and a reasonable chance of cure with acceptable morbidity