Background::Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.Methods::The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.Results::Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs. 15.5 months, P = 0.0005) and OS (11.1 months vs. not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs. 15.5 months, P = 0.0532) rather than OS ( P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs. 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS ( P = 0.0052) but not OS ( P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[φ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4). Conclusions::Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

Objective:To investigate the characteristics and the management of male genital lichen sclerosus (MGLSc)accompanied by urethral carcinoma.Methods:A retrospective analysis was performed on 16MGLSc accompanied by urethral carcinoma patients who were referred to Shanghai Sixth People’s Hospital between June 2000 and August 2019. The average age was 53.7 (45-69) years. All of the patients had a mean history of MGLSc 15(6-35) years, anterior urethral stricture received urethral dilatation and other inappropriate urethrotomy treatment for 10 (8-15) years. There were 5 cases of solid mass 4.5 (3-7) cm in scrotum, accompanied by obviously pain. There were 11 cases of infective masses 6(4-10)cm in the perineum, and the masses were ulcerated with purulent secretions and residue-like pus mixed with necrotic tissues draining from the wounds. Urethrocutaneous fistula developed in 9 cases, and the secretions in the fistula cannot heal. The diseased tissue was confirmed by pathology as the metastasis of invasive urothelial carcinoma in 12 patients and urethral squamous cell carcinoma in 4 patients. 9 cases of tumor invaded corpus spongiosum or corpus cavernosum, 5 cases invaded corpus spongiosum or corpus cavernosum, with enlarged firm one side inguinal node. 2 cases of tumor invaded corpus cavernosum, beyond prostatic capsule and bladder neck, bilateral palpable inguinal lymph nodes metastasis were found, one case found tumor involved the left testis. 9 cases were T 2-3N 0M 0, 5 cases T 2-3N 1M 0, 1 case T 3N 2M 0, 1 case T 4N 2M 1. 5 patients with substantial tumors located in the scrotum, penile-sparing scrotum tumor, urethral tumor resection and urethrostomy was performed in 2 patients. Partial phallectomy, urethral tumor resection and perineal urethrostomy were performed in 3 patients. 11 patients with urethral cancer complicated with perineal infectious mass, 2 patients underwent extensive resection of the tumor and suprapubic cystostomy. 8 cases with perineal tumor infection complicated with urethrocutaneous fistulas formation, of which 2 patients received perineal mass, urethral tumor, fistula resection and suprapubic cystostomy, 4 patients with unilateral inguinal lymph node metastasis and received perineal mass, urethral tumor, fistula, lymph node resection and suprapubic cystostomy. 2 patients with bilateral inguinal node metastasis underwent total phallectomy and urethrectomy, inguinal lymph node resection and suprapubic cystostomy. One case of perineal infectious mass with urethral cutaneous fistula and unilateral inguinal lymph node metastasis (T 2-3N 1M 0) gave up tumor resection. Results:The pathological examination of surgical resection of the glans and urethra showed typical MGLSc manifestations as epithelial keratinization, basal cell vacuoles degeneration, dermis lymphocyte infiltration. The pathological examination of the surgical excised diseased urethra and surrounding tumor tissue showed invasive urothelial carcinoma in 12 patients. Immunohistochemical staining showed positive expression of P53, Ki-67 and GATA3. 4 patients of urethral squamous carcinoma and immunohistochemical staining showed positive expression of Ki-67, P40 and GATA3. All patients received cisplatin combined with gemcitabine chemotherapy for an average of 4.8 (2-6)courses and received local radiotherapy (50-70Gy/5w). The mean postoperative survival time of the 16 patients was 26 (3-48) months, and the survival time of urethral transitional cell carcinoma and squamous cell carcinoma was 29 (18-48) months and 18 (3-24) months, respectively. All patients died of tumor metastasis, with 6 patients of lung metastsis, 2 patients of lumbar and bone metastasis, 3 patients of liver metastasis, 2 patients of brain metastasis and 3 patients of lung combined with bone metastasis.Conclusions:MGLSc can cause urethal stricture and urethral carcinoma. The clinical manifestations are dysuria, urinary tumor, repeated infection and urethral fistula. Tumor excision and urinary diversion are common surgical methods. Urethral transitional cell carcinoma and squamous cell carcinoma are common pathological types. Postoperative combined radiotherapy and chemotherapy can be used, but the overall prognosis is poor.

Objective To analyze the donor site complications of male patients with long segment anterior urethral strictures that underwent urethroplasty by using a long-strip lingual mucosal grafts (LMG) six months later.Methods Between August 2006 and December 2014,a total of 81 patients with long segment anterior urethral stricture underwent a procedure of urethroplasty using a long-strip LMG.The mean patients' age was 41.2 years (range 18-74) and the mean urethral stricture length was 12.1 cm (range,8-20 cm),a single LMG was more than 9 cm.Two techniques of urethroplasty were performed:One-sided dorsal graft augmentation urethroplasty was performed in 70 patients,12 of the 70 patients underwent urethroplasty by using a LMG in addition to a BMG,owing to the presence of very long strictures;Dorsal patch graft urethroplasty was performed in 11 patients.Results Of the 81 patients a single long-strip LMG with length of 9-11 cm was used in 52 patients,LMG measured ≥12 cm in 17,and LMG combined with buccal mucosal graft (BMG) in 12.The mean follow-up period was 41 months (range,15-86 months) postoperatively.The overall urethroplasty success rate was 82.7％.Six months after the operation,28 patients (34.6％) reported a minimal to moderate difficulty in fine motor movement of the tongue (difficulty with spitting tiny fish bones).Among these 28,22 patients (27.2 ％) had associated numbness over the donor site,10 patients (12.3％) had parageusia,and 11 patients (13.6％) reported slurring of speech.The donor site complications occurred higher in patients with LMG length ≥ 12 cm (14/29) than those patients with LMG length ＜ 12 cm (14/52)(x2 =19.049,P ＜0.01).At 12 months,5 patients (6.2％)reported minimal difficulty in fine motor movement of the tongue,and reduced to 1 patient at 24 months.Conclusions The donor side complications after long-strip lingual mucosal graft for the treatment of longsegment anterior urethral strictures are primarily limited to the first postoperative year,the incidence of complications appeared to be related to the length of the harvested graft.

Objective To evaluate the outcome of various operative selection for treating posterior urethral stricture via transperineal approach.Methods The clinical data of 5 000 patients with posterior urethral stricture or obstruction from January 1990 to January 2017 were analyzed retrospectively.All patients were male.The age of those patients ranged from 18 months to 77 years old,mean 36.6 years old.Pelvic crush inju.ry caused by car accident occurred in 2010 cases.Falling injury occurred in 1680 cases.Pelvic compressed injury occurred in 1 310 cases.Accompanied visceral damage occurred in 2 590 cases,including the liver and spleen rupture in 920 cases,lower limb fracture in 1 200 cases.2 200 cases accepted urethral realignment under emergency.2 800 cases were treated with pubic cystostomy.All patients were undergone a retrograde and voiding urethrogram.562 patients accepted urethral ultrasongraphy,and 2 448 patients accepted urethroscopy.204 patients accepted MRI examination.The mean stricture length was 4.3 cm,ranged from 1.8 to 8.6 cm.Posterior urethral stricture was found in 810(16.2％)cases.The complete olstruction of posterior urethra was found in 4 190 (83.8％) cases,of which the length of the distraction defects≤3 cm was found in 2 650(53.0％) cases and the length of the distraction defects ＞ 3 cm was found in 1 540 (30.8％) cases.Bladder calculi was found in 2 300 cases.The perineal fistula or abscess was noticed in 290 cases.False passage was found in 460 cases.Urethra rectum fistula was found in 160 cases.Bladder neck open was noticed in 89 cases.Repairing was performed via a simple anastomosis after urethral mobilization in 1 700 patients,via separation of the corporeal bodies in 1 302 patients,via separation of the corporeal bodies and inferior pubectomy in 1 910 patients and via scrotal skin flap urethroplasty in 68 patients.Pull-through operation was performed in 20 patients.Results Postoperative follow-up were conducted from 6 to 72 months with average duration of 23 months.The overall successive results after operation was 92.2％(4 608/5 000),which the Q was more than 15 ml/s.The successive rate of urethroplasty were 97％(1 649/1 700) in simple anastomosis;93％ (1 211/1 302) in separation of the corporeal bodies;88％ (1 680/1 910) in separation of the corporeal bodies and inferior puberctomy;78％ (53/68) in scrotal skin flap urethroplasty and 83％ (15/18) in pull-through operation.The successive rate were 96％ (778/810) in posterior urethral stricture;95％ (2 517/2 650)in distraction with the length of obstruction less than 3 cm and 86％ (1 324/1 540) in distraction with the length of obstruction more than 3 cm.Conclusions The transperineal end to end anastomotic urethroplasty has become the first-line therapy for posterior urethral atresia.The length of the strictures or distraction defect which is lower than 3 cm is much more successfully corrected.

Objective    To explore the effect of pulmonary arterial hypertension on the children with functional single ventricle in the early period after Fontan operation. Methods    Forty-three children with pulmonary arterial hypertension after Fontan operation were enrolled in our department between January 2015 and December 2016. There were 24 males and 19 females at a median age of 4.3 years ranging from 2.5 to 4.8 years. The pulmonary arterial pressure was evaluated by cardiac catheterization. There were 23 children diagnosed without pulmonary hypertension (a non-PAH group) including 16 males and 7 females, while 20 patients were diagnosed with pulmonary hypertension (a PAH group) including 8 males and 12 females. Postoperative parameters related to outcomes were compared between the two groups. Results    There was no death in the non-PAH group, but the mortality of children in the PAH group was 20.0% (4/20， χ2=5.34, P=0.02). The central venous pressure (t=–2.50, P=0.02), N-terminal prohormone of brain natriuretic peptide (NT-proBNP, Z=–3.50, P<0.01), peritoneal dialysis rate (χ2=5.40, P=0.02), incidence of arrhythmia (χ2=4.40, P=0.03) in the PAH group were significantly higher than those of the non-PAH group. The early postoperative utilization rate of pulmonary vascular targeting agents in the PAH group was significantly higher than that in the non-PAH group (χ2=6.30, P=0.04). Conclusion    Pulmonary arterial hypertension is one of the most important factors which influence the early postoperative prognosis of children with functional single ventricle after Fontan operation.

Objective To evaluate the risk factors,diagnostic index of the restrictive right ventricle physiology(rRV) and the impact of the mid-term outcome of the patients.Methods Eighty patients(30 in rRV group and 50 in non-rRV group) undergoing TOF repair admitted in our department from Oct 2011 to May 2012 were studied.Perioperative clinical data were collected and echo data were recorded after operation.Mixed linear regression for repeated measures was used to compare the variables and analyze the correlations.Results Patients in rRV group were younger with longer cardiopulmonary bypass(CPB) time,aortic cross clamp time,ventilation time,intensive care unit and hospital stay compared with those in non-rRV group(P<0.01,respectively).The younger patients with longer CPB time had high risk of rRV by logistic regression analysis.Within 7 days post operation,the increase of saturation of venous oxygenation and decrease of oxygen extraction ration were slower in rRV group than those in non-rRV group(P<0.05,respectively).Lactate decreased in both groups,but was higher in rRV group throughout the 7 days(P=0.03).NT-proBNP was higher in rRV group throughout the 7 days than that in non-rRV group.NT-proBNP≥4750pg/ml often indicated the patients in the state of rRV.CRP slightly increased in 1-2 days post operation,and decreased thereafter,and the decrease was slower in rRV group(P=0.08).With regard to the mid-term outcome,there was no significant differences in the incidences of the obstruction of the right ventricle outflow and main pulmonary artery,the stenosis of the branch of pulmonary artery and the degree of the pulmonary valve regurgitation.Conclusion rRV is associated with significantly higher levels of NT-proBNP and CRP.The incidence of rRV correlates with age on operation and positively correlates with CPB time.NT-proBNP would be regarded as an indicator of the incidence of rRV.The study indicated the rRV would have impact on the early outcome of the patients but there was no significant effect on mid-term outcome.

Objective To study the value of flexible cystoscopy in diagnosing posterior urethral strictures resulting from pelvic fracture and the pain score of the examination. Methods Between 2014 and 2015, 120 male patients with pelvic fracture urethral distraction defect were evaluated by cystoscopy before surgery. In this study, flexible cystoscopy was used in 87 patients, 33 patients received conventional rigid cystoscopy. The cystoscopy was introduced into the posterior urethra and the area was evaluated for the length of the proximal urethra and any possible fistulas, false passages, calculi or displacement of the posterior urethra. The patient’s pain feeling was recorded during the examination, 24 hrs after cystoscopy examination. The pain feeling result was achieved by visual analogue pain scale. Results Severe allergic reaction or obvious discomfort did not occur in any patients after cystoscopy. By comparing the data obtained from lfexible cystoscopy to those from conventional urethrography, the rate of detection in other abnormalities was higher in lfexible cystoscopy than in conventional urethrography. 21, 5, 7 and 5 patients were detected with calculus, posterior urethral structure damage, false passage and ifstula respectively. In comparison, the abnormalities were only observed in 3, 2, 3 and 1 patients respectively through conventional urethrography imaging. However, the pain feeling of the flexible cystoscopy is better than the convenional rigid cystoscopy. The statistical difference was found in the pain feeling score during the examination and later after the examination. Conclusions Flexible cystoscopy is a safe and valuable procedure in the evaluation of the posterior urethra in patients with pelvic fracture urethral distraction defect before surgery.

Objective To explore the appropriate management for girls with posttraumatic urethral stricture or loss secondary to pelvic fracture.Methods Between January 2009 and December 2015,a total of 20 girls,mean age of 9.5 years (range 2-14 years),whose posttraumatic urethral stricture associated with urethrovaginal fistula were treated using a variety of procedures.The mean urethral stricture or loss length was 2.6 cm (range 2-4 cm).Six patients presented with vaginal distal stricture and associated with a large hydrocolpos in the proximal vagina.Of the 20 girls,urethroplasty was performed using labial pedicle flap or vulvar flap in l0 patients,using a bladder flap tube in 5 girls with total urethral loss,using vaginal flap in 5 cases.Colpoplasty using island vulvar skin flaps or hydrocolpos vagina were performed in the 6 patients associated with vaginal stricture during urethroplasty.Results There were no serious complications postoperatively.The mean follow-up period was 41 months (range 12-70 months) postoperatively.The overall anatomical success rate was 90％ (18/20) and the functional success rate was 70％ (14 / 20).Of 10 patients underwent pedicle labial or an island flap of vulva urethroplasty,2 patients were recurrent,and 2 patients present stress incontinence.Five patients underwent urethral reconstruction using a bladder flap tube and voiding well postoperatively,of which stress incontinence appeared in 2.All 5 patients who underwent vaginal flap urethroplasty could void normally and continently.The hydrocolpos disappeared in all 6 patients with vaginal distal severe stricture.Conclusions A differential surgical repair strategy should be determined by fistula location,stricture length and vaginal condition for posttraumatic urethral stricture associated with urethrovaginal fistula in girls.It is probably good choice to reconstruct distal urethra and vagina using a large hydrocolpos in the proximal vagina for the treatment of coexisting strictures of urethra and vagina.

Objective    To investigate somatic growth of children undergoing stageⅡ Fontan procedure. Methods    Clinical data of 152 children who underwent stageⅡ Fontan procedure in Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine between January 2012 and December 2015 were reviewed. There were 84 males and 68 females at age of 4-16 years. The weight and height of those children in each operative stage were assessed, and WHO Z-score was obtained to describe the pattern of growth of the children. Results    Mean weight for age Z-score (WAZ) and height for age Z-score (HAZ) were –0.73 and 0.06 at birth, –1.27±1.37 and –1.27±1.72 before Glenn procedure, –0.47±1.08 and –0.69±1.17 before Fontan procedure, –0.42±1.18 and –0.39±1.48 at follow-up, respectively. A significant decline (P<0.05) in WAZ and HAZ was found before Glenn procedure. After the Glenn procedure, there was significant catch-up growth (P<0.05). The WAZ was stabilized after Fontan procedure, while the HAZ was reversed (P<0.05) continually. Conclusion    The somatic growth is impaired in children with stageⅡ Fontan procedure. There is a trough of growth before Glenn procedure. Although catch-up growth occurs after Glenn procedure, low body weight and growth retardation remain at follow-up. Effective interventions such as more intensive nutritional strategies before Glenn procedure should be targeted at those children in the future, so as to improve their growth.

Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation. However, acquired resistance, defined as tumor progression after initial response, seems to be an inevitable consequence of this treatment approach. Clinical modes of EGFR-TKI failure are classified into three types: dramatic progression, gradual progression and local progression. A threonine-to-methionine substitution (T790M) in exon 20 of the EGFR gene is the most common mechanism of resistance. Other mechanisms of resistance include MET amplification, epithelial to mesenchymal transition, small cell transformation, and PIK3CA mutation. This brief comment will provide an overview of the complex and heterogeneous problem of acquired resistance to EGFR-TKI therapy in NSCLC, and the clinical treatment options and new targeted drugs overcoming EGFR-TKI acquired resistance.