[Clinical characteristics of patients with colon complications after necrotizing pancreatitis: a retrospective cohort study].

Objective: To investigate the clinical characteristics of colon complications in patients with necrotizing pancreatitis(NP). Methods: The clinical data of 403 patients with NP admitted to the Department of General Surgery,Xuanwu Hospital, Capital Medical University from January 2014 to December 2021 were retrospectively analyzed. There were 273 males and 130 females,aged (49.4±15.4) years(range: 18 to 90 years). Among them,there were 199 cases of biliary pancreatitis,110 cases of hyperlipidemic pancreatitis,and 94 cases of pancreatitis caused by other causes. A multidisciplinary diagnosis and treatment model was used to diagnose and treat patients. Depending on whether the patients had colon complications,they were divided into colon complications group and noncolon complications group. Patients with colon complications were treated with anti-infection therapy,parental nutritional support,keeping the drainage tube unobstructed,and terminal ileostomy. The clinical results of the two groups were compared and analyzed using a 1∶1 propensity score match(PSM) method. The t test,χ2 test, or rank-sum test was used to analyze data between groups,respectively. Results: The incidence of colon complications was 13.2%(53/403),including 15 cases of colon obstruction,23 cases of colon fistula,and 21 cases of colon hemorrhage. After PSM,the baseline and clinical characteristics at admission of the two groups of patients were comparable (all P>0.05). In terms of clinical outcome,compared to patients with NP without colon complications,the number of patients with colon complications who received minimally invasive intervention(88.7%(47/53) vs. 69.8%(37/53),χ2=5.736,P=0.030),the number of minimally invasive interventions (M(IQR))(2(2) vs. 1(1), Z=4.638,P=0.034),the number of patients with multiple organ failure(45.3%(24/53) vs. 32.1%(17/53),χ2=4.826,P=0.041),and the number of extrapancreatic infections(79.2%(42/53) vs. 60.4%(32/53),χ2=4.476,P=0.034) increased significantly. The time required for enteral nutrition support(8(30)days vs. 2(10) days, Z=-3.048, P=0.002), parental nutritional support(32(37)days vs. 17(19)days, Z=-2.592, P=0.009),the length of stay in the ICU(24(51)days vs. 18(31)days, Z=-2.268, P=0.002),and the total length of stay (43(52)days vs. 30(40)days, Z=-2.589, P=0.013) were also significantly prolonged. However,mortality rates in the two groups were similar(37.7%(20/53) vs. 34.0%(18/53),χ2=0.164,P=0.840). Conclusions: Colonic complications in NP patients are not rare,which can lead to prolonged hospitalization and increased surgical intervention. Active surgical intervention can help improve the prognosis of these patients.

[Cytomegalovirus detoxification and associated factors among preschool children in Yi'nan County].

Objective: To investigate cytomegalovirus detoxification and associated factors among preschool children in Yinan County, Shandong Province. Methods: Two kindergartens were selected from the county and township of Yinan respectively. A total of 250 children were investigated in October 2018. Case information was obtained through the child's guardian. Saliva samples of children and their mothers were collected for cytomegalovirus realtime-PCR detection.The status of CMV detoxification of children was explored and the associated factors were analyzed. Results: A total of 242 preschool children were investigated, and the detoxification rate of cytomegalovirus among them was 22.31% (54/242, 95%CI: 17.0%-27.6%). Logistic regression analysis showed that the rate of detoxification was higher in children whose mothers were cytomegalovirus detoxified (OR=12.39, 95%CI:1.73-88.65)and whose school was located in the county (OR=3.58, 95%CI:1.34-9.55). Conclusions: The detoxification rate of cytomegalovirus in preschool children is high, and there is mutual transmission between children and mothers. Women of childbearing age should pay attention to prevent congenital cytomegalovirus infection when they come into contact with children.

[Survival time and related factors on HIV/AIDS patients in Guizhou province from 1995 to 2018].

Objective: To examine the survival time and related factors on HIV/AIDS patients in Guizhou province from 1995 to 2018. Methods: A retrospective cohort study was conducted to analyze the HIV/AIDS case from 1995 to 2018 in Guizhou province with data gathered from the "Chinese National Comprehensive HIV/AIDS Prevention and care Information system". Survival rate was calculated by life table and survival time was estimated by Kaplan-Meier. Related factors on survival time were analyzed by Cox regression model. Results: A total of 53 232 HIV/AIDS cases were included in the study, with the mortality rate as 8.53/100 person-years (14 210/166 679.18), median survival time as 10.20 (95%CI: 9.91-10.48) years, and survival rates of 1, 5, 10 and 20 years as 0.85, 0.68, 0.51, 0.36, 0.19 respectively. Results from the multivariate Cox regression analysis showed that factors as: being male (compared with females, aHR=0.757, 95%CI: 0.727-0.788), with antiviral treatment (ART) (compared with those without ART, aHR=0.173, 95%CI: 0.165-0.181), CD(4)<200 cells/µl[compared with CD(4)(+)T cells (CD(4)) ≥200 cells/µl, aHR=0.410, 95%CI: 0.387-0.435], age ≥45 (compared with age<45, aHR=1.506, 95%CI: 1.193-1.901), illiterate (compared with having high school education or above, aHR=0.904, 95%CI: 0.832-0.982), unmarried (compared with divorced or widowed, aHR=0.896, 95%CI: 0.848-0.946), through heterosexual transmission (compared with homosexual transmission, aHR=0.555, 95%CI: 0.487-0.632), ethnic minorities (compared with Hans, aHR=1.185, 95%CI: 1.114-1.262), and farmers/migrant workers (compared with domestic/unemployed,aHR=0.874, 95%CI: 0.834-0.916,) etc., were related to the survival time of HIV/AIDS, in Guizhou province. Conclusions: The mortality rate of HIV/AIDS in Guizhou province appeared relatively high, but with no obvious downward trend seen in the last years. Factors as being male, age ≥45, low education level, ethnic minorities, CD(4)<200 cells/µl were identified as related to the HIV/AIDS survival time. We would suggest that treatment and follow-up management programs should be strengthened to improve the quality of life among these patients.

Identification and evaluation of outcome measurement instruments in pyoderma gangrenosum: a systematic review.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that causes tissue destruction and subsequent painful ulcers. To date, there are no core domains or instruments for assessing PG severity in clinical trials, and current treatment paradigms rely on outcome measurements that have not been well characterized in the literature. OBJECTIVES: To perform two systematic reviews that (i) identify the outcome measurement instruments used in PG clinical trials and their corresponding domains and (ii) identify any associated validation studies and evaluate their measurement properties and methodological quality. METHODS: We systematically searched the MEDLINE and Embase databases for PG outcome measurement instruments. We also systematically searched for PG instrument validation studies. We evaluated the measurement properties and methodological quality of validation studies using the 2018 COSMIN Risk of Bias checklist. RESULTS: In total, seven clinical trials were included. These studies utilized a total of 20 different instruments, including 11 physician-reported instruments, eight patient-reported instruments and one composite instrument. Among these, 85% of the instruments lacked any validation data. Of the remaining three validated instruments (speed of healing, physician global assessment and resolution of inflammation), methodological quality was not available for half of the COSMIN categories. CONCLUSIONS: We identified 17 non-validated outcome measurement instruments used in PG clinical trials. We conclude that PG validation studies are required for existing instruments, and new instruments need to be developed to inform the consensus process for the development of a core outcome set for PG. What is already known about this topic? Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that has been characterized by multiple outcome measurement instruments in clinical trials. However, there is no consensus on the most validated and appropriate outcome measurement instruments. What does this study add? This study identifies and evaluates 20 unique outcome measurement instruments for PG in the literature. Of these 20, 17 lack any instrument validation data, highlighting the need for future studies. What are the clinical implications of this work? Despite the current use of several outcome measurement instruments, future studies should explore the validation surrounding these instruments, as no instruments can currently be recommended.

[Clinical study of different surgical approaches in laparoscopic debridement for patients with infected pancreatic necrosis].

Objective: To examine the indications and effects of different surgical approaches in laparoscopic debridement for patients with infected pancreatic necrosis(IPN). Methods: The clinical data of 213 IPN patients treated by laparoscopic debridement at Department of General Surgery,Xuanwu Hospital, Capital Medical University from June 2012 to February 2019 were retrospectively analyzed.The therapeutic effects were summarized and analyzed according to different surgical approaches. There were 123 cases in retroperitoneal approach group, including 73 males and 50 females, aging of (51.3±12.4)years; 59 cases in omental sac approach group, including 32 males and 27 females, aging of (48.3±14.2)years; 23 cases in combined approach group, including 13 males and 10 females,aging of(54.3±19.7)years;8 cases in digestive tract approach group, including 5 males and 3 females, aging of(50.2±12.5)years. Results: The time from onset to operation in retro-peritoneal, omental sac, combined and digestive tract approach groups were (44.3±22.8), (47.3±24.3), (52.6±21.2), (51.2±30.1)days, respectively; the operation time was (52.3±26.4), (64.3±29.2), (82.8±24.7), (78.2±38.1) minutes respectively; the median bleeding volume was 18, 33, 42 and 30 ml, respectively; and the first time to eat after operation was (2.5±1.6),(3.8±1.8),(3.7±2.0),(8.4±3.9) days, respectively. The incidence of complications (Clavien-Dindo grade Ⅲ and above)was 10.6%(13/123),10.2% (6/59),17.4%(4/23),1/8 and the mortality was 4.9%(6/123),3.4%(2/59),4.3%(1/23)and 0,respectively.The overall mortality of all patients was 4.2%(9/213).The levels of inflammatory factors were significantly lower in all groups 7 days after operation than before,and no patients was converted to open surgery. Conclusion: Individualized selection of the optimal laparoscopic debridement approach of pancreatic necrosis plays an important role in improving the efficacy and prognosis of IPN patients.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

ACE-inhibitor suppresses the apoptosis induced by endoplasmic reticulum stress in renal tubular in experimental diabetic rats.

AIMS: The aim of the present study was to investigate the role of the endoplasmic reticulum stress and apoptosis in experimental diabetic nephropathy. The effects of ACE inhibitor on the endoplasmic reticulum stress and apoptosis were also assessed. METHODS: Diabetes was induced in male Sprague-Dawley rats by injection with streptozotocin at 60 mg/kg i .p. Diabetic rats were then randomly assigned into control (untreated) or treatment of an ACE inhibitor, perindopril, for 24 weeks. Tubulointerstitial injury was assessed by histopathology. Tubule apoptosis was detected by TUNEL assay. Endoplasmic reticulum stress associated proteins expression of glucose-regulated protein-78 (GRP78/BiP), phospho-eukaryotic initiation factor 2 alpha (eIF2 alpha), phospho-pancreatic ER kinase (PERK) and caspase-12 was assessed by immunohistochemistry and Western blots. RESULTS: There were more TUNEL-positive nuclei in diabetic kidneys than in control kidneys. At 24 weeks, experimental diabetes was associated with a considerable increase in protein expression of GRP78, phospho-eIF2 alpha, phospho-PERK, and caspase-12 in the tubulointestitium. ACE inhibitor not only attenuated the apoptosis but also reduced the overexpression of these endoplasmic reticulum stress associated proteins in tubulointestitium of diabetic rats. CONCLUSIONS: Increased tubular apoptosis in experimental diabetic rats is attenuated by blockade of the renin-angiotensin system with an ACE inhibitor, which might be in an association with reduced endoplasmic reticulum stress.

A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia.

To evaluate the safety and efficacy of infliximab administered with gemcitabine to treat cancer cachexia and to explore a functional measure of clinical benefit, investigators involved in this multicenter, phase II, placebo-controlled study randomized 89 patients with stage II-IV pancreatic cancer and cachexia to receive either placebo or 3 mg/ kg or 5 mg/kg of infliximab at weeks 0, 2, and 4 and then every 4 weeks to week 24; patients also received 1,000 mg/m2 of gemcitabine weekly from weeks 0-6 and then for 3 of every 4 weeks until their disease progressed. The primary endpoint was change in lean body mass (LBM) at 8 weeks from baseline; major secondary endpoints included overall survival, progression-free survival, Karnofsky performance status, and 6-minute walk test distance. In addition, quality of life was measured. The mean change in LBM at 8 weeks was +0.4 kg for patients receiving placebo, +0.3 kg for those receiving 3 mg/kg of infliximab, and +1.7 kg for those receiving 5 mg/kg of infliximab. No statistically significant differences in LBM or secondary endpoints were observed among the groups. Safety findings were similar in all groups. Adding infliximab to gemcitabine to treat cachexia in advanced pancreatic cancer patients was not associated with statistically significant differences in safety or efficacy when compared with placebo.

Phase II study of the American Brachytherapy Society guidelines for the use of high-dose rate brachytherapy in the treatment of cervical carcinoma: is 45-50.4 Gy radiochemotherapy plus 31.8 Gy in six fractions high-dose rate brachytherapy tolerable?

In 2000, the American Brachytherapy Society (ABS) published incompletely evaluated guidelines for curative chemoradiation and high-dose rate (HDR) brachytherapy for cervical cancer: our aim was to assess guideline tolerability in an Asian population. From 2000, all stage I-IVA cervical carcinoma patients were treated following ABS guidelines. Early disease (FIGO stage I/II <4 cm) received 45 Gy whole-pelvis external-beam radiation (EBRT) at 1.8 Gy/fraction, while advanced-stage disease received 50.4 Gy: no central shielding was used. All patients were planned to receive chemotherapy during EBRT, cisplatin 40 mg/m(2) weekly. All patients received 31.8-Gy HDR brachytherapy (six fractions of 5.3 Gy/fraction) to point A via three-channel applicators. Radiotherapy was completed within 8 weeks. Toxicity scoring used Common Toxicity Criteria. Nineteen of 21 (90.4%) patients (8 early, 13 advanced stage) received planned radiation, and 85.7% received planned chemotherapy. Median follow-up was 24 months (range 9-50 months). Three-year overall survival (S) was 79.1% and disease-free survival (DFS) was 64.8%. S/DFS for early and advanced stage was 85.7%/85.7% and 73.3%/47.1%, respectively. Complete response (CR) was achieved by 85.7% of patients, partial response 14.3%. For those in CR, there were no local failures. Acute cystitis occurred in 23.8%, proctitis 4.8%, and gastroenteritis 47.6%. Late cystitis occurred in 9.5%, gastroenteritis 4.8%, and genitourinary fistula (in the presence of progressive disease) 4.8%. No grade 3/4 treatment-related toxicity occurred. The ABS guidelines were well tolerated and efficacious in our study, although longer follow-up is required. Further studies are warranted to validate safety and efficacy of the recommendations.

Volatilization of heavy metals during incineration of municipal solid wastes.

Incineration experiments with MSW, which had been impregnated with heavy metals, were presented to obtain information on the volatilization behavior of the elements cadmium(Cd), lead (Pb), and zinc (Zn) under different conditions. Experiments were carried out in a bubbling fluid bed system connected to a customized inductively coupled plasma optical emission spectroscopy (ICP-OES) for analyzing metals in the flue gas. The results indicated that the combustion temperature, the gas atmosphere, and the chlorine content in the flue gas could affect the volatilization behavior of heavy metals. In the fluidized bed combustion, a large surface area was provided by the bed sand particles, and they may act as absorbents for the gaseous ash-forming compound. Comparer with the metals Cd and Pb, the vaporization of Zn was low. The formation of stable compounds such as ZnO x Al2O3 could greatly decrease the metals volatilization. The presence of chlorine would enhance the volatilization of heavy metals by increasing the formation of metal chlorides. However, when the oxygen content was high, the chlorinating reaction was kinetically hindered, which heavy metals release would be delayed.

Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10.

PURPOSE: To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT. METHODS AND MATERIALS: Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT. RESULTS: Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%. CONCLUSION: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.

Growth in use of lipid-lowering therapies: are we targeting the right patients?

BACKGROUND: Prescription drug spending has been rising at > 10% per year, with volume of use (rather than price) being the primary driver for that growth. Concern exists that industry marketing has led to increased use of medications by patients with marginal indications. OBJECTIVE: To determine whether the increase in the number of patients receiving lipid-lowering therapy represents a shift away from treatment of patients at highest cardiovascular (CV) risk towards patients in lower risk categories. STUDY DESIGN AND METHODS: Cardiovascular risk criteria adapted from guidelines were applied to an administrative database of medical and pharmaceutical claims for 1997 and 1999 that included managed care plan enrollees in 22 states. Patients were assigned to 1 of 7 categories representing CV risk based on documentation of CV disease/risk factors, with category 1 and 2 indicating the highest risk group (secondary prevention). The odds of the treated population being in the highest risk during 1997 versus 1999 were calculated, adjusting for age and sex. RESULTS: Patients treated with lipid medications in the study population increased from 5% in 1997 to 8% in 1999. During the same period, the percentage of treated patients in categories 1 through 6 rose from 17% to 21%. The odds of the treated population being in the highest risk group did not differ significantly between the 2 years (odds ratio (OR) = 0.99; 95% confidence interval, (CI) 0.96-1.01; P = .40). CONCLUSIONS: Despite an increase in the percentage of patients receiving lipid-lowering therapy from 1997 to 1999, treatment rates rose modestly across all categories. Greater overall use did not appear to be associated with a shift in use towards patients with less CV risk.

Sildenafil citrate effectively reverses sexual dysfunction induced by three-dimensional conformal radiation therapy.

OBJECTIVES: We evaluated the response of sildenafil citrate in patients with prostate cancer treated with three-dimensional conformal radiation therapy (3DCRT) whose sexual function (SF) was known prior to therapy initiation. METHODS: From March 1996 to April 1999, 24 men with median age of 68 years (range 51 to 77) had 3DCRT for localized prostate cancer (median prescribed dose to the planning target volume of 70.2 Gy). These men started taking sildenafil for relief of sexual dysfunction at a median time of 1 year after completing 3DCRT. We used the self-administered O'Leary Brief Sexual Function Inventory to evaluate in series SF and overall satisfaction at three time points. These points were (a) before initiation of all therapies (3DCRT or hormonal treatment [HT]) for prostate cancer, (b) before starting sildenafil (50 mg or 100 mg) but after completion of all therapies, and (c) at least 2 months afterward. Rates of SF were based on the number of men responding to a given question. We tested for significance of these two interventions to change SF by applying the Wilcoxon sign rank test. RESULTS: Prior to all treatments, 20 (87%) of 23 men were sexually potent, with 8 (36%) of 22 fully potent (little or no difficulty for penetration at intercourse). After 3DCRT with or without HT and prior to sildenafil use, 13 (65%) of the 20 potent patients remained potent, with only 2 (11%) of 19 being fully potent. The use of sildenafil citrate resulted in 21 (91%) of 23 men being potent, with 7 (30%) being fully potent. In 16 men responding to the satisfaction question, 10 (63%) and 12 (75%) were mixed to very satisfied with their sex life before 3DCRT with or without HT and after sildenafil citrate use, respectively. This response corresponded to potency and satisfaction scores significantly decreasing and subsequently increasing on average by one unit after 3DCRT and sildenafil citrate use, respectively (P <0.05). CONCLUSIONS: In men receiving 3DCRT for prostate cancer, these data indicate that sildenafil citrate is effective for restoring SF and associated satisfaction back to baseline before treatment.

Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose.

OBJECTIVES: To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses. METHODS: Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled. RESULTS: Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level (P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose (P=0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses (P=0.048). Severe late RT-related complications were infrequent and did not correlate with dose. CONCLUSIONS: In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.

Twice-daily fractionation of external irradiation with brachytherapy and chemotherapy in carcinoma of the cervix with positive para-aortic lymph nodes: Phase II study of the Radiation Therapy Oncology Group 92-10.

PURPOSE: The purpose of this study was to evaluate the toxicity and efficacy of twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. METHODS AND MATERIALS: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para-aortics at 4- to 6-h intervals, 5 days per week. The total external radiation doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48 Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to the known metastatic para-aortic site. One or two intracavitary applications were performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75 mg/m2, days 1 and 22) and 5-FU (1000 mg/m2/24 h x 4 days; days 1 and 22) were given for two or three cycles. RESULTS: Twenty-nine patients with clinical Stages I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were enrolled in this study. Hyperfractionated external radiotherapy was completed in 86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29), 31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no brachytherapy, one had three applications, and one had five HDR applications. Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5 toxicity occurred and the patient died from a myocardial infarction from chemotherapy and radiotherapy colitis during her course of therapy. The median follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year and 47% at 2 years. The probability of local-regional failure was 38% at 1 year and 49% at 2 years. The probability of disease failure at any site was 45% at 1 year and 59% at 2 years. CONCLUSION: The results suggest that twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of Grade 4 nonhematologic toxicity. One patient died from complications of therapy. Radiotherapy was completed per protocol in 69%. The survival estimates appear no better than standard fractionation radiotherapy without chemotherapy. Additional follow-up is necessary for long-term survival estimates.

Radiation alone for carcinoma of the vagina: variation in response related to the location of the primary tumor.

BACKGROUND: A retrospective study of 40 patients with histologically confirmed carcinoma of the vagina is reported. The patients were treated by radiation alone (a combination of external beam therapy and implants) between October 1969 and September 1991 at the Medical College of Virginia Hospital in Richmond. METHODS: Thirty-three patients (82%) had squamous cell carcinoma, 2 patients (7%) had adenocarcinoma, and 2 patients (5%) had poorly differentiated cancers (1 melanoma and 1 leiomyosarcoma). The patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system; there were 13 patients (33%) in Stage 1, 21 (52%) in Stage II, 4 (10%) in Stage III, and 2 (5%) in Stage IV. Thirty-six patients (90%) were treated with external beam therapy and some combination of implant: cylinder, ovoid, or interstitial implants with iodine-125 or iridium-192 (afterloading). Only 4 patients (10%) received treatment by implant only. RESULTS: Based on their response, two groups of patients were identified. Group I had 23 patients with tumors predominantly located in the proximal half of the vagina; there were 8 patients in Stage I, 11 in Stage II, 3 in Stage III, and 1 in Stage IV. Of these, three patients failed: one each in Stages III and IV and one Stage II patient was salvaged by surgery. Three patients died due to unrelated causes but with local control. The 5-year actuarial survival in this group was 81%. Group II had 17 patients with tumors located in the mid to distal half of the vagina; there were 5 patients in Stage I, 10 in Stage II, and 2 in Stage IV. Ten patients failed. Eight patients in Stage II had persistent disease, were lost to follow-up, and are presumed dead. Two patients with Stage IV disease also had inadequate local control. The overall actuarial survival in the distal group was 41%, which was significantly worse than the proximal group (81%), at a P value of 0.05. CONCLUSIONS: This study discusses the curability of carcinoma of the vagina based on its anatomic location when predominantly similar treatment techniques and radiation doses were applied to either the proximal or the distal part of the vagina, those with cancer in the proximal half had better survival (81%) than those whose cancer was in the distal half (41%).