Protocolized management of infants with congenital diaphragmatic hernia: effect on survival

Background/Purpose

In 2006, we introduced a new protocol for congenital diaphragmatic hernia (CDH) management featuring nitric oxide in the delivery room, gentle ventilation, lower criteria for extracorporeal membrane oxygenation (ECMO), and appropriately timed operative repair on ECMO. Our goals were to assess outcomes after institution of this protocol and to compare results with historical controls.

Methods

Charts were reviewed of all newborns admitted to a large metropolitan children's hospital from 2002 to 2009 with a diagnosis of CDH. Data were recorded regarding delivery, ECMO, operative repair, length of stay, comorbidities/anomalies, complications, and survival. Postprotocol outcomes were compared to those from the preprotocol era and to data from the international CDH Registry.

Results

Comparison of the protocolized group (n = 43) to the historical group (n = 51) revealed no significant differences in gestational age, birth weight, Apgar scores, or comorbidities. New treatment strategies substantially improved survival to discharge (67% preprotocol, 88% postprotocol; P = .015). Among ECMO patients, survival increased to 82% (20% preprotocol; P = .002).

Conclusions

Our new protocol significantly improved survival to discharge for newborns with CDH. Institution of such a protocol is valuable in improving outcomes for patients with CDH and merits consideration for widespread adoption.     

舒尼替尼治疗转移性肾癌的疗效和安全性分析:单中心37例总结

目的 评价舒尼替尼治疗转移性肾细胞癌的疗效和安全性.方法 2008年6月至2010年4月37例转移性肾细胞癌患者接受舒尼替尼治疗.其中男28例,女9例.年龄17～74岁,中位年龄52岁.行根治性肾切除手术33例,肾穿刺活检3例,腋窝转移淋巴结穿刺活检1例.vonHippel-Lindau综合征患者2例.肾透明细胞癌36例,其中伴颗粒细胞成分1例、伴肉瘤样分化4例,肾乳头状细胞癌1例.一线治疗30例,细胞因子或索拉非尼治疗进展后二线治疗7例.其中34例采用4/2方案,即口服舒尼替尼50.0 mg/d 4周,停用2周,6周为1个周期;3例予口服37.5 mg/d持续治疗,直至疾病进展或者出现不可耐受的不良反应.结果 中位随访时间12个月(8个周期).34例患者治疗2周期以上,可进行疗效评估.根据RECIST标准评价最佳疗效,部分缓解9例(26.5%),疾病稳定24例(70.6%),疾病进展1例(2.9%).客观反应率26.5%,疾病控制率97.1%.1年生存率95.8%(23/24),1年无进展生存率62.5%(15/24).主要不良反应包括血小板减少30例(81.1%)、甲状腺功能异常18/22例(81.8%)、手足反应27例(73.0%),白细胞减少23例(62.2%)、高血压18例(48.6%)等.大多数不良反应为1～2级,3级以上不良反应包括血小板降低8例(21.6%)、甲状腺功能异常4/22例(18.2%)、手足反应4例(10.8%)、血磷降低4例(10.8%)和腹泻2例(5.4%)等.10例(27.0%)在治疗过程中减量或停药,1例因严重乏力不能耐受终止治疗.通过对症支持,减量或停药,不良反应可控制并耐受.结论 舒尼替尼一线及二线治疗晚期转移性肾细胞癌可取得较高的疾病控制率,不良反应发生率多数轻而易耐受,严重不良反应较少且可控.

Abstract：

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.     

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy

PurposeThe effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC.MethodsWe retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m² at baseline were considered obese, whereas those with a BMI <30 kg/m² were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure.ResultsAmong 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42–13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47–15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10⁻⁴–0.81; p = 0.025).ConclusionsObese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity.     

Evaluation of congenital diaphragmatic hernia in a tertiary health center of a developing country: management and survival

Aim The purpose was to evaluate the diagnosis and efficacy of management of congenital diaphragmatic hernia (CDH) in a tertiary health center of a developing country. Methods Forty-six children aged from 1 day to 7 years were studied. Parameters studied were age, sex, clinical features, and management. Results Fifty-six percent of patients presented in the neonatal period; however, none of them presented on the first day of life. The majority (91.3%) of patients had left-sided CDH. Respiratory distress was the most common clinical feature observed (91.3%). Chest X-ray confirmed the diagnosis in 82.6% of patients, and contrast study was needed in the remaining 17.4%. The survival rate was 87%. It was better in patients presenting late than those presenting in the early neonatal period. Stabilization in the preoperative period improved survival. Not using a chest tube had no adverse effect on survival. Conclusion The relatively increased survival rate of CDH in a tertiary health center of a developing country is attributed to delayed arrival to the center. Respiratory infections compound the survival. More studies are needed before it can be safely said that not using a chest tube has no adverse outcome. Late presentation has been associated with varied manifestations, hence proper clinical evaluation, a high index of suspicion and adequate management, which includes imaging and surgery after stabilization, gives excellent results.     

Papillary Thyroid Carcinoma: Factors Influencing Recurrence and Survival

Background The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. Materials and Methods From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. Results Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2–17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). Conclusion Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.     

Depth of tumor invasion in locally advanced rectal cancer correlates with patients’ prognosis: The usefulness of elastic stain for its measurement

Purpose The relationship between the prognosis and the extent of colorectal carcinoma (CRC) is still unclear. As a simple parameter of the local invasion of CRC, we assessed the extent of tumor invasion beyond the outer border of the muscularis propria (MP). Methods We examined 147 cases of CRC using a slight modification of the procedure established by the Japanese Society for Cancer of the Colon and Rectum. For the statistical analysis, the patients were divided into two groups, namely, a “shallow” group and a “deep” group, using a specific cut-off value (COV). A multivariate analysis to identify independent prognostic factors was performed. Results Significant differences in the 5-year survival rate were observed between the “shallow” and “deep” groups in 39 cases of rectal carcinoma (COV 4 mm; 72.4% vs. 30.0%, hazard ratio = 3.204), but not observed in 147 cases of CRC. In addition, the outcome for patients with “deep” cancer in the lower rectum was markedly worse than that for patients with “shallow” cancer (COV 4 mm; 81.8% vs. 12.5%, hazard ratio = 5.371). Conclusions The depth of tumor invasion beyond the MP is thus considered to be an important prognostic factor for patients with T3/T4 rectal carcinoma, especially in the lower rectum. A careful follow-up is required for the patients with rectal carcinoma that has invaded more than 4 mm beyond the MP.     

Prognosis and Determinants of Outcome Following Locoregional or Distant Recurrence in Patients with Cutaneous Melanoma

Objective Information on prognosis for patients with cutaneous melanoma after locoregional or distant recurrence is sparse and controversial. The aim of this study was to analyze factors influencing outcome after the development of a first relapse. Methods Information was extracted from the Sydney Melanoma Unit database for 873 melanoma patients with American Joint Committee on Cancer (AJCC) Stage I and II disease treated between 1960 and 2002 who relapsed following treatment of their primary melanoma. Clinical and pathologic factors predicting survival were analyzed using the Cox proportional hazards regression model. Results Initial presentation of recurrence was local: 95 patients (10.9%), in transit: 86 patients (9.9%), regional lymph node: 300 patients (34.4%), and distant: 392 patients (44.9%). Independent prognostic factors for survival of the 481 patients with only locoregional recurrence were type of recurrence, primary tumor ulceration, and patient age. Predictors for longer survival in the 392 patients with distant metastasis at the time of first presentation with recurrence were lung vs other sites and diagnosis of relapse after 1990 compared with diagnosis before 1980. Conclusions The type of recurrence is the most important prognostic factor in melanoma patients who relapse. Primary tumor ulceration is the most important pathologic predictor. The results of this study suggest that management of distant metastases may have improved over the last 25 years, but many confounders and improved staging techniques make assessment of this unreliable.     

An analysis of radical prostatectomy in advanced stage and high-grade prostate cancer

OBJECTIVES: To clarify the role of radical prostatectomy (RP) in the treatment of locally advanced and high-grade prostate cancer. METHODS: Literature search of Medline publications on surgery for locally advanced and high-grade prostate cancer. RESULTS: In patients with locally advanced disease, the cancer-specific survival rate after RP at 5- and 10-yr follow-up was 85-100% and 57-91.6%, respectively. The overall survival rate at 5 and 10 yr was>75% and 60%, respectively. In patients with high-grade prostate cancer (Gleason score> or =8), the biochemical recurrence-free survival after RP at 5 and 10 yr of follow-up was 51% and 39%, respectively. Nomograms and modern imaging techniques are useful in predicting pathologic stage, presence of positive lymph nodes, or seminal vesicle involvement. These allow physicians to recognise those patients with locally advanced disease who are most likely to benefit from surgical treatment. Downgraded and organ- or specimen-confined high-grade tumours can have a good prognosis after surgery. The prostate-specific antigen value and the percent positive biopsy cores can be helpful in identifying men with high-grade prostate cancer most likely to benefit from RP. CONCLUSIONS: It is likely that surgery has a role in the treatment of locally advanced and high-grade tumours. However, it is necessary and urgent to have randomised trials assessing survival and quality of life when RP is and is not included in the multimodality treatment.     

Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas

BACKGROUND: Patients with occult metastasis or locally nonresectable pancreatic cancer found during surgical exploration have a limited life expectancy. We sought to define markers in these patients that could predict survival and thus aid decision making for selection of the most appropriate therapeutic palliative option. METHODS: In a prospective 4-year single-center study, 136 consecutive patients with obstructive pancreatic cancer and intraoperative diagnosis of nonresectable or disseminated pancreatic cancer underwent a palliative surgical bypass procedure. Potential factors predicting survival were evaluated. RESULTS: Ninety-eight patients had metastatic disease and 38 locally advanced disease. Surgical morbidity rate was 16 %, re-operation rate 1%, and overall in-hospital mortality 4%. Univariate analysis showed American Society of Anesthesiologists (ASA) score, pain, operation time, presence of metastasis, and levels of leukocytes, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were associated significantly with survival. The multivariate analysis identified ASA score, presence of liver metastasis, pain, CA 19-9, and CEA levels as independent indicators for poor survival. Patients with none or 1 of these risk factors had a median survival of 13.5 months, whereas patients with 4 or 5 risk factors had a median survival of 3.5 months. CONCLUSIONS: The clinical markers identified predict poor outcome for patients with palliative bypass surgery and therefore aid the appropriate selection of either surgical bypass or endoscopic stenting in these patients.     

Plasma exchange before surgery for left ventricular assist device implantation

Abstract:  Left ventricular assist device (LVAD) implantation in end-stage heart failure patients is frequently associated with hemorrhagic complications requiring reoperation. The preoperative coagulopathic profile includes prolonged prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time; platelet dysfunction; decreased coagulation factor activity; and increased inflammatory markers. We compare outcomes in LVAD patients treated with preoperative plasma exchange with concurrent, nonrandomized control patients. We reviewed data from 68 consecutive elective patients who received LVADs at our institution. Thirty-five received LVADs after preoperative plasma exchange (replacement of one plasma volume of fresh frozen plasma), and 33 received LVADs without plasma exchange. Groups were comparable in age, sex, body weight, New York Heart Association class, intra-aortic balloon pump insertion, cardiac index, pulmonary capillary wedge pressure, creatinine, total bilirubin, hemoglobin levels, PT, international normalized ratio, PTT, and platelet count. Early mortality was lower in the plasma exchange group (0% [0/35] vs. 18% [6/33], P  = 0.026), and postoperative chest tube drainage decreased by 33% ( P  = not significant). Blood transfusion requirements were similar.Perioperative mortality decreased in patients treated with plasma exchange before LVAD implantation.