Does segmentectomy really preserve the pulmonary function better than lobectomy for patients with early-stage lung cancer?

Purpose

Recently, segmentectomy has been considered as an alternative to lobectomy in early peripheral non-small lung cancer (NSCLC); however, controversy has remained regarding the long-term functional advantage after segmentectomy. The aim of this study was to analyze the postoperative lung function after segmentectomy and lobectomy for non-small cell lung cancer.

Methods

Patients with p-T1aN0M0 NSCLC who had undergone segmentectomy (n = 37) or lobectomy (n = 33) were retrospectively analyzed. The ratios of postoperative to preoperative forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were defined as the recovery rates. The radiological lung volume and weight were evaluated before and more than 6 months after surgery, and the postoperative values were compared with the predicted values that were calculated from the preoperative values, subtracting the resected lobes or segments.

Results

The clinical characteristics, including the preoperative lung function showed no significant differences between the groups. No statistical differences were recognized in the trend lines for recovery ratios of FVC and FEV1.0 (P = 0.96 and P = 0.33). The recovery ratios for radiologic lung volume and weight showed no significant differences (P = 0.46 and P = 0.22). The postoperative lung volume and weight were almost the same as the predicted values after segmentectomy, whereas those after lobectomy were significantly higher than the predicted values.

Conclusions

No functional advantage for segmentectomy was observed during long-term follow-up, possibly due to compensatory lung growth after lobectomy.

     

Does cardiac resynchronisation therapy improve survival and quality of life in patients with end-stage heart failure?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether bi-ventricular pacing, also referred to as cardiac resynchronisation therapy (CRT), improves survival and quality of life in patients with severe (NYHA III/IV) symptomatic heart failure. Cardiac pacing can be achieved by stimulation of the right ventricle, left ventricle (LV) or by bi-ventricular pacing. This best evidence topic considers only bi-ventricular pacing. This involves placement of pacing leads in the right ventricle, epicardially on the LV with a lead typically placed in a branch of the coronary sinus and, unless the patient is in permanent atrial fibrillation, in the right atrium. Bi-ventricular pacing allows the optimisation of atrio-ventricular timing and resynchronisation of septal and postero-lateral left ventricular contraction. Symptomatic heart failure has a high morbidity and a poor prognosis. Patients with dyspnoea at rest or on minimal exertion (NYHA III/IV) are at high risk of death due to progressive heart failure, while those with less severe symptoms are more likely to experience sudden cardiac death. Up to 50% of patients with NYHA class III/IV symptoms have a prolonged QRS duration (>120 ms) on 12-lead ECG (usually in a LBBB pattern). This intra-ventricular conduction delay is a surrogate marker of mechanical dyssynchrony (an uncoordinated regional contraction-relaxation pattern) and is associated with reduced cardiac output and increased mortality. Bi-ventricular pacing can reduce the delay in activation of the LV free wall found in many patients with LV systolic dysfunction, thereby improving mechanical synchrony and cardiac output. It may also reduce pre-systolic mitral regurgitation. Three hundred and fifty-six papers were identified using the search method outlined, nine randomised controlled trials and a meta-analysis in addition to published guidelines presented the best evidence to answer the clinical question. Current best available evidence suggests that in patients with left ventricular systolic dysfunction (LVEF or=120 ms), and NYHA class III or IV symptoms despite optimal pharmacological therapy, bi-ventricular pacing significantly reduces the number of hospitalisations from heart failure, improves functional status (NYHA class, peak oxygen uptake and exercise tolerance) and improves health related quality of life. The CARE-HF study also demonstrated a reduction in mortality from progressive heart failure and all-cause mortality.     

Does initial choice of antimicrobial therapy affect length of stay for patients with complicated intra-abdominal infections?

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were > 18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.     

Efficacy and safety of combined therapy with tamsulosin and tolterodine in female patients with a maximal flow rate less than 12?ml/s

Introduction and hypothesis  

We assessed the effect of tamsulosin HCl (0.2 mg) with or without tolterodine extended release (2 mg) on female patients with a maximal flow rate (Qmax) less than 12 ml/s who were suspected of having functional bladder outlet obstruction.     

The use of the score for neonatal acute physiology-perinatal extension (SNAPPE II) in perforated necrotizing enterocolitis: could it guide therapy in newborns less than 1500 g?

Background

Only a handful of clinical parameters other than body weight are used in managing LBW newborns with perforated necrotizing enterocolitis (NEC). Here, we determined clinical use of score for neonatal acute physiology-perinatal extension (SNAPPE II) score in the surgical decision, peritoneal drain (PD) vs PD + laparotomy in low birth weight (LBW) newborns with perforated NEC.

Patients and Method

A retrospective study of all neonates weighing less than 1500 g with the diagnosis of perforated NEC between 2000 and 2006 was performed. Patients were categorized in 2 groups—PD alone vs PD + laparotomy. The SNAPPE score was calculated at various days of clinical evolution. The primary outcome of mortality was used, and comparisons using univariate and multivariate analyses were performed.

Results

Of 39 patients identified, 20 were treated with PD alone, whereas 19 had PD and laparotomy. The mean gestational age (25.6 vs 26.6 weeks) and the mean birth weight (795 vs 910 g) were comparable (P > .05). There were no differences between PD group and LAP group with regard to SNAPPE scores calculated on the day of admission (P = .057), the day before the drain insertion (P = .167) and the day after the drain insertion (P = .66). When considering survival as the dependent variable while controlling for the treatment assignment, the modified SNAPPE score after PD drain insertion in group PD was significantly higher than in the PD + laparotomy group (21.4 vs 9.47; P = .009).

Conclusion

The modified SNAPPE score is a good predictor of mortality after the PD insertion. A post-PD insertion, high SNAPPE value was correlated with increased mortality regardless of an additional laparotomy. External validation of the modified SNAPPE score in a large patient population is required before its use in guiding treatment decisions.     

What proportion of patients with an ostomy (for diverticulitis) get reversed?

A common operation for patients with complicated sigmoid diverticulitis is resection and placement of an ostomy (Hartmann procedure). This population-based study examines that proportion of ostomates who undergo reversal. In the California inpatient file, patients admitted for acute diverticulitis in 1995 were identified, including a subset that had surgical resection. Data regarding receipt of ostomy were obtained (4-year follow-up). Demographics and clinical data (procedure, ostomy reversal, time to reversal, comorbidity score, and complications) were collected. In 1995, 11,582 admissions for diverticulitis occurred in California. Of these, 24.2 per cent (n = 2808) underwent surgery at admission; 88.9 per cent were sigmoid/left colectomies; and 41.7 per cent had a Hartmann procedure. Patients with ostomies were older (P = 0.0004) and male (P = 0.03). Median comobidity score was the same for patients with or without an ostomy. Of the 1176 patients who had the Hartmann procedure, 65 per cent underwent reversal (mean 143 days). A larger proportion of men than women had their ostomies reversed (74.5% vs 55.9%, respectively, P < 0.0001). Median comorbidity scores for both groups were low, 0 for those reversed and 1 for nonreversed. Our study shows that although the majority of patients had their ostomies reversed, over 35 per cent did not at 4-year follow-up. Further studies are required to evaluate how this rate may be improved.     

Model for End-Stage Liver Disease (MELD) score system to evaluate patients with viral hepatitis on the waiting list: better than the Child-Turcotte-Pugh (CTP) system?

BACKGROUND: The Model for End-Stage Liver Disease (MELD), based on creatinine, bilirubin, and International normalized ratio (INR), has been shown to be superior to the Child-Turcotte-Pugh (CTP) score in predicting 3-month mortality among patients on the transplant waiting list due to end-stage liver disease (ESLD). An additional advantage of MELD is the possibility to add "adjustment points" for exceptional patients at risk for death because of liver disease not identified by changes in the used parameters, as occurs in the case of hepatocellular carcinoma (HCC). Although it is useful, MELD has some important limitations: There are no differences for patients with or without ascites, and for the absence of other laboratory parameters involved in the etiology of disease. In this study, we evaluated dropouts of patients on the waiting list for orthotopic liver transplantation (OLT) based upon the characteristics of these subjects before and after introduction of the MELD score. METHODS: All patients on the OLT waiting list from June 1, 2006 to June 30, 2007 were enrolled in the MELD group (A) and evaluated with CHILD and MELD score, while those listed from January 1, 2004 to May 31, 2005 were enrolled in pre-MELD group (B) to be evaluated with CHILD. In these subjects we assessed the drop out frequency and waiting time and we compared the results to assess possible differences (U Mann-Whitney Test; P<.05). RESULTS: The total number of patients included in this study was 176: 116 patients in Group A and 60 in Group B. We had a drop-out frequency of 21% with a median of 9+/-6 S.E. months in Group A, while 9% with a median of 15+/-8 months S.E. in Group B. The dropout frequencies were as follows: Group A--16 deaths (1 HCC--15 disease complications) while in Group B we had 13 drop outs, 10 exitus (4 HCC and 6 disease complications) and three exclusions for nonmedical reasons. In Group A we had a higher number of deaths due to disease complications than in group B (P<.05). Further, we had 32 OLTx in Group A and 45 in Group B. Survival rate did not show any differences between the two groups while number needed to harm was 11. CONCLUSIONS: The use of MELD score in this group of patients produced an advantage for HCC, but seemed to cutoff patients with viral hepatitis complications during the waiting time. Particularly, about one in every 11 patients may receive an harm using this score system. Other parameters should be introduced as adjustment points to make the MELD score suitable also for patients with infectious liver diseases.     

Does metformin improve the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor treatment for patients with advanced non-small-cell lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether metformin improved the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer. A total of 99 papers were found using the reported search, of which 4 represented the best evidence to answer this clinical question. The authors, journal, publication date, country, study type, treatment regimen, relevant outcomes and results of these papers are tabulated. We concluded that the addition of metformin to EGFR-TKI might improve the survival of patients with EGFR-mutated non-small-cell lung cancer and diabetes mellitus type 2. However, for non-diabetic non-small-cell lung cancer patients with EGFR mutation, the efficiency of additional metformin in EGFR-TKI treatment remains unclear because of the conflicting results of only 2 available studies.     

Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)--what is the procedure of choice in critically ill patients?

Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so.     

Comparison of inhibitors of renin–angiotensin–aldosterone system (RAS) and combination therapy of steroids plus RAS inhibitors for patients with advanced immunoglobulin A nephropathy and impaired renal function

Background  

The adaptation of steroid therapy and the effect of renin–angiotensin–aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial.     

Can simvastatin improve erectile function and health‐related quality of life in men aged >40 years with erectile dysfunction? Rationale and design of the Erectile Dysfunction and Statins (EDS) Trial [ISRCTN66772971]1

What’s known on the subject? and What will the study add? Erectile dysfunction is often associated with endothelial dysfunction. It is also recognized as a marker for underlying vascular disease. This study tests the hypothesis that statin therapy may improve erectile function and also reduce the risk of future cardiovascular events via a reduction in serum cholesterol and by improving endothelial function. The study will also determine whether the treatment improves quality of life related to sexual function.

OBJECTIVE

? To describe the rationale and design of the Erectile Dysfunction and Statins (EDS) Trial which aims to evaluate the effectiveness of simvastatin on erectile function and health‐related quality of life in men aged ≥40 years with erectile dysfunction.

PATIENTS AND METHODS

? The study is a randomized, double‐blind, placebo‐controlled trial to test the hypotheses that statins improve endothelial function and reduce cholesterol and may improve erectile function in men with untreated erectile dysfunction (ED). ? Study subjects are men ≥40 years who are not receiving lipid‐lowering or anti‐hypertensive medication and have no other cardiovascular disease (CVD) risk factors. ? Eligible men with untreated ED are randomized to double‐blind treatment with 40 mg simvastatin or placebo once daily for 6 months. ? Data are collected at baseline, mid‐trial and at the final follow‐up visit at 30 weeks. ? The main outcome is erectile function measured by the five‐item version of the International Index of Erectile Function. Secondary outcomes include sexual‐health‐related quality of life and endothelial function.

RESULTS

? Ten general practices have been recruited in the east of England. ? We have randomized 173 men for a power of 90% to assess the main outcome. ? To date there have been no serious unexpected adverse events. ? Study findings will be available in September 2011.

CONCLUSION

? If simvastatin improves erectile function it would provide an inexpensive treatment for ED suitable for most men, and reduce the risk of future CVD.     

A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5°

Purpose

High tibial osteotomy (HTO) is a recommended concomitant surgery when treating cartilage lesions of the medial femoral condyle (MFC). Varus deformities of 5° and more were considered an indication for HTO in patients with cartilage defects. This study compares clinical outcome in patients with ACI and concomitant varus deformity of <5° with or without additional HTO.

Methods

43 patients with isolated cartilage defect of the MFC and varus deformity between 1° and 5° (mean age 39.14 ± 8.35 years; mean varus deformity 2.84 ± 1.19°) were included (follow-up 71.88 ± 23.99 months). Group A (n = 19) was treated with ACI and additional HTO; group B (n = 24) received ACI only. Survival rate in terms of absence of the need of reintervention was defined as main outcome parameter. In the subgroup without reintervention, functional outcome (KOOS and WOMAC) was evaluated.

Results

Overall rate of reintervention was 12 (27.9 %). Survival was significantly higher in group A (group A 89.5 %, group B 58.33 %; p = 0.023). Although a trend for better clinical outcome was observed for group A in the subgroup without reintervention, this observation lacked statistical significance (KOOS_symptoms group A 73.23, group B 59.64; p = 0.274).

Conclusion

While there is general consensus for treating varus deformities of >5° in patients with cartilage lesions of the medial femoral condyle, HTO also leads to a reduced rate of reinterventions and longer survival rates in patients with varus deformities of <5°.     

Should mediastinal nodal dissection be routinely undertaken in patients with peripheral small-sized (2 cm or less) lung cancer? Retrospective analysis of 225 patients.

OBJECTIVE: We retrospectively reviewed nodal status of the patients with peripheral small-sized lung cancer grouped by cell type and tumor size to evaluate the necessity of systematic nodal dissection in this group of patients. METHODS: From 1973 to 1998, 1713 patients underwent pulmonary resection for primary lung cancer in Kanazawa University. Among them, 225 patients (13.1%) with peripheral small-sized (2 cm or less) lung cancer underwent lobectomy and systematic nodal dissection were retrospectively reviewed. The maximum diameter of the tumor was measured on formalin-fixed surgical specimens. RESULTS: The histological types were adenocarcinoma in 170 (75.6%), squamous cell carcinoma in 20 (8.9%), small cell carcinoma in 19 (8.4%) and others in 16 (7.1%). Among 170 adenocarcinoma patients, 38 (22.4%) showed hilar or mediastinal lymph node metastases. No mediastinal lymph node metastasis was encountered in all squamous cell carcinoma (n = 20), adenocarcinoma < or = 1 cm (n = 16), small cell carcinoma < or = 1 cm (n = 4), and adenocarcinoma of Noguchi's classification type A or B (n = 24). CONCLUSIONS: Mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized lung cancer fulfilling these criteria: (1) squamous cell carcinoma < or = 2 cm; (2) adenocarcinoma < or = 1 cm; (3) localized bronchioloalveolar carcinoma < or = 2 cm without foci of active fibroblastic proliferation in histology (Noguchi's classification type A or B adenocarcinoma); (4) small cell carcinoma < or = 1 cm. Candidates fulfilling above criteria were 28.4% (64/225) of small-sized lung cancer and 10.9% of stage IA patients. The establishment of a universally accepted therapeutic strategy for small-sized lung cancer is indispensable in the clinical spread of various sort of limited resections.     

Outcomes of Triple-Negative Breast Cancers (TNBC) Compared with Non-TNBC: Does the Survival Vary for All Stages?

Background

Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior and worse outcomes. In a study at a tertiary care breast unit in a developing country, clinico-pathological attributes and outcomes of patients with TNBC were compared with (c.w.) ER, PR, and/or HER2 expressing tumors (non-TNBC).

Patients and methods

Medical records of 1213 consecutive breast cancer patients managed during 2004–2010 were reviewed. An evaluable cohort of 705 patients with complete treatment and follow-up (median 36 months) information was thus identified. Patients were categorized per ER, PR & HER2 status into TNBC, and ER/PR+ and/or HER2+ groups. Clinico-pathological parameters, response to NACT, and OS & DFS were compared between TNBC and non-TNBC groups.

Results

TNBC patients (n = 249) comprised 35.3 % of the study cohort (n = 705), and were significantly younger than non-TNBC patients (mean age 49.1 ± 11.2y c.w. 51.8 ± 11.3, p = 0.02). The TNM stage at presentation was similar in the two groups (Stage I and II—37 % c.w. 44.3 %, Stage III—47.5 % c.w. 39.5 %, Stage IV—15.5 % c.w. 16.2 % in TNBC c.w. Non-TNBC; p = 0.09). Tumor size (5.7 ± 2.9 cm TNBC c.w. 5.4 ± 2.8 cm non-TNBC, p = 0.22) was similar but lymph nodal (cN) metastases were more frequent in TNBC (77.3 % c.w. 69.8 %; p = 0.03). TNBC had higher histologic grade (97.1 % gr II/III in TNBC c.w. 91.2 % non-TNBC, p = 0.01) and higher incidence of LVI (20.4 % in TNBC c.w. 13.5 %, p = 0.03). Patient groups received similar multi-disciplinary surgical, radiation, and systemic treatment. Comparable proportion of patients in 2 groups were treated with NACT (42 % c.w. 38 %), which resulted in pathological complete response (pCR) in 27.5 % TNBC patients c.w. 17.1 % non-TNBC patients (p = 0.04). Both OS (81.8 ± 4.52 c.w. 97.90 ± 3.87 months, p < 0.001) and DFS (89.2 ± 5.1 c.w. 113.8 ± 4.3 months, p < 0.001) were shorter in TNBC than non-TNBC group. On stage-wise comparison, OS differed significantly only in stage III (47.4 ± 5.3 months in TNBC c.w. 74.5 ± 4.4 in non-TNBC; p < 0.001). Univariate and multivariate analyses revealed tumor stage and IHC subtyping into TNBC c.w. non-TNBC as most important factors predictive of survival.

Conclusions

TNBC occurred at younger age and exhibited aggressive pathology as compared to non-TNBC patients. Although patients with TNBC exhibited better chemo-sensitivity, they had worse DFS and OS compared to the non-TNBC patients. The survival of Stage III TNBC patients was significantly worse compared to non-TNBC group; while in stages I, II, and IV, survival were not significantly different.

     

Does ductal adenocarcinoma of the prostate (DA) have any prognostic impact on patients with de novo metastatic prostate cancer?

Background: The prognostic value of ductal adenocarcinoma of the prostate (DA) in nonmetastatic prostate cancer (PCa) has been identified in many studies. However, it remains unknown whether DA is an adverse prognostic factor in metastatic PCa (mPCa). Method: Data from 634 mPCa patients histopathologically documented with DA or/and acinar adenocarcinoma of the prostate in our center between 2012 and 2018 were retrospectively analyzed. Propensity score matching (PSM) was used to balance the baseline features. Data from the Surveillance, Epidemiology, and End Results (SEER) database were utilized to validate our findings. Castration-resistant PCa-free survival (CFS), overall survival (OS), and cancer-specific survival (CSS) were set as endpoints. Results: DA was confirmed in 35 of 634 (5.5%) patients. Among the DA-positive patients, 7 of 35 (20%) and 28 of 35 (80%) harbored high (DA ≥ 50%) and low (DA < 50%) DA components, respectively. DA was not associated with poorer median CFS (mCFS) or median OS (mOS) either before PSM (mCFS: 16.9 vs 18.4 month, P = .814; mOS: 42.0 vs 70.1 month, P = .796) or after PSM (mCFS: 16.9 vs 16.9 month, P = .949; mOS: 42.0 vs 79.9 month, P = .960). Likewise, in the SEER data, DA-positive patients (n = 15 153) shared similar median CSS (25.0 vs 28.0 month, P = .206) and OS (26.0 vs 35.0 month, P = .095) with DA-negative patients (n = 70). No prognostic difference was found between patients with high and low DA components. Conclusion: We conducted the first study investigating the prognostic value of DA in de novo mPCa. DA was not associated with adverse clinical outcomes in mPCa patients. These findings are helpful for prognostic evaluation, treatment decision making and counseling in mPCa patients.