The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines

The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot. While a therapeutic antibody, Bamlanivimab, decreases binding affinity to Delta variant by ~20 fold, it fully lost binding to Lambda variant. Structural modeling of complexes of RBD with human receptor, Angiotensin Converting Enzyme 2 (ACE2), and Bamlanivimab suggest the potential basis of the change of binding. The data suggest possible danger and a potential surge of Lambda variant in near future.

501Y.V2 and 501Y.V3 variants of SARS-CoV-2 lose binding to Bamlanivimab in vitro

We generated several versions of the receptor binding domain (RBD) of the Spike protein with mutations existing within newly emerging variants from South Africa and Brazil. We found that the mutant RBD with K417N, E484K, and N501Y exchanges has higher binding affinity to the human receptor compared to the wildtype RBD. This mutated version of RBD also completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro.

The basis of a more contagious 501Y.V1 variant of SARS-COV-2

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing a world-wide pandemic. A variant of SARS-COV-2 (20I/501Y.V1) recently discovered in the United Kingdom has a single mutation from N501 to Y501 within the receptor binding domain (Y501-RBD), of the Spike protein of the virus. This variant is much more contagious than the original version (N501-RBD). We found that this mutated version of RBD binds to human Angiotensin Converting Enzyme 2 (ACE2) a ~10 times more tightly than the native version (N501-RBD). Modeling analysis showed that the N501Y mutation would allow a potential aromatic ring-ring interaction and an additional hydrogen bond between the RBD and ACE2. However, sera from individuals immunized with the Pfizer-BioNTech vaccine still efficiently block the binding of Y501-RBD to ACE2 though with a slight compromised manner by comparison with their ability to inhibit binding to ACE2 of N501-RBD. This may raise the concern whether therapeutic anti-RBD antibodies used to treat COVID-19 patients are still efficacious. Nevertheless, a therapeutic antibody, Bamlanivimab, still binds to the Y501-RBD as efficiently as its binds to N501-RBD.

Clinical characteristics and prognostic analysis of young patients with stage ⅠB-ⅢA cervical cancer / 中华放射肿瘤学杂志

Objective To investigate the clinicopathological features,survival,and the impact of postoperative adjuvant radiotherapy on the ovarian function in patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer.Methods One hundred and eighty-six patients who were admitted to our hospital from 2000 to 2011 were retrospectively analyzed.An equal number of patients older than 35 years of age with cervical cancer within the same period were used as stage-marched controls.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used for pairwise comparison and univariate prognostic analyses.The Cox proportional hazards model was used for multivariate prognostic analyses.Results The patients less than or equal to 35 years of age had a significantly higher incidence of non-squamous carcinoma but significantly lower incidence rates of deep stromal invasion and lymph-vascular space invasion (LVSI) compared with the control group (P =0.000;P =0.008;P =0.000).Though young patients had significantly higher 5-year disease-free survival (DFS) and overall survival (OS) rates than the control group (93.7％ vs.84.5％,P=0.005;96.1％ vs.89.5％,P=0.033),age was not an independent prognostic factor (P =0.202;P =0.950).Among patients less than or equal to 35 years of age,lymph node metastasis and LVSI were independent prognostic factors for DFS (P =0.000;P =0.000),while LVSI and initial tumor size were independent prognostic factors for OS (P =0.000;P =0.000).There was no significant difference in the incidence of normal ovarian function between young patients treated with and without adjuvant radiotherapy after ovarian transposition (63％ vs.73％,P =0.422).Conclusions Patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer have a better prognosis than the control group.However,age is not an independent prognostic factor.Postoperative adjuvant radiotherapy will not impair the function of transposed ovaries.

Double primary carcinoma of endometrial carcinoma and colorec-tal carcinoma: retrospective analysis of 34 cases and discussion of its relationship with Lynch syndrome / 中国肿瘤临床

Objective:To approach the clinicopathologic characteristics, treatment modalities, and prognosis of the patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma and analyze the relationship between this disease and Lynch syndrome. Methods:The clinicopathologic and follow-up data of 34 cases with double primary carcinoma of endometrial carci-noma and colorectal carcinoma treated in Cancer Hospital of Chinese Academy of Medical Sciences were reviewed. Results:The medi-an age of the 34 patients was 51.5 years old (ranging from 39 to 76). Twenty-two of the total cases (22/34, 64.7%) had tumor family his-tory. The pathologic results indicated that 79.4%(27/34) was endometrioid adenocarcinoma. In the 34 cases, 33 were treated by surgical procedure. Of the 33 cases undergoing surgery, 17 patients with endometrial carcinoma and 19 with colorectal carcinoma received fur-ther adjuvant treatment of chemotherapy and/or radiotherapy. The 2-and 5-year survival rates were 84.3%and 63.1%in the 34 cases, respectively. Conclusion:The age of onset is earlier in the patients with double primary carcinoma than in those with sporadic colorec-tal carcinoma. Some cases have cancer family history, and their survival rates are similar to those of the patients with sporadic colorec-tum carcinoma. Diagnosis of some patients with double primary carcinoma may be in line with Lynch syndrome.

[Evaluation of postoperative bladder function and prognosis after modified nerve sparing radical hysterectomy].

OBJECTIVE: To compare the nerve plane sparing radical hysterectomy (NPSRH) with conventional radical hysterectomy (CRH) in terms of postoperative bladder function and prognosis. METHODS: One hundred and two patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ib1-IIa2 cervical cancer were treated by open NPSRH (study group) from January 2008 to March 2013. During the same time periods, two hundred and four patients who underwent open CRH were randomly selected as the control group. Age, pathological type and FIGO stage were matched. RESULTS: The median operation time in NPSRH group and CRH group were 268.8 and 242.4 minutes, respectively (P < 0.01). The median hospital stay were 14.6 and 17.2 days (P < 0.01). The median volume of blood loss in the two groups were respectively 394 and 450 ml (P > 0.05). The blood transfusion rate was respectively 46.1% (47/102) and 41.7% (85/204; P > 0.05). The rate of postoperative complications were not significantly difference [14.7% (15/102) vs 11.8% (24/204), P > 0.05]. The median duration of catheterization was 9.1 and 15.2 days between two groups (P < 0.01). Eighty-five patients in NPSRH group and one hundred and sixty-seven patients in CRH group completed the telephone interview about the long-term bladder function. The incidence of long-term urinary frequency [14.1% (12/85) vs 33.5% (56/167)], urinary incontinence [36.5% (31/85) vs 54.5% (91/167) ], urinary retention [23.5% (20/85) vs 38.9% (65/167) ] and straining to void [10.6% (9/85) vs 40.7% (68/167)], there were significantly lower in NPSRH group than those in CRH group ( all P < 0.05). The rate of recurrence was 10.8% (11/102) in NPSRH group and 12.2% (25/204) in CRH group (P = 0.707). Three-year recurrence-free survival (RFS) estimate was 88.5% in NPSRH group and 91.1% in CRH group (P = 0.746). Three-year overall survival (OS) estimate was 93.7% in NPSRH group and 96.3% in CRH group (P = 0.701). The univariate analysis shown that pathological type, lymph node metastases, and lymph-vascular space invasion (LVSI) presented the trend for a worst 3-year RFS and OS (P < 0.05) . The multivariate analyses shown that both pathological type and lymph node metastases were associated with a worst 3-year RFS (P < 0.05) . Lymph node metastases was a significant independent predictor of 3-year OS (P = 0.001) . NPSRH was not a significant independent predictor by Cox regression model analyses. CONCLUSION: NPSRH contributes to bladder function recovery without compromising survival.

Clinical analysis of ovarian preservation for stageⅠendometrial carcinomas in women aged 40 years and younger / 中华妇产科杂志

Objective To investigate the safety of ovarian preservation for stage Ⅰ endometrial carcinomas in women aged 40 years and younger.Methods Seventy-five cases of stage Ⅰ endometrial cancer aged 40 years and younger from Jan 1999 to Jan 2012 were treated in Cancer Hospital , Chinese Academy of Medical Sciences.They were further divided into two groups:20 patients who underwent ovarian preservation (group A) and 55 patients who underwent oophorectomy (group B).Clinical and pathological recordings of these patients were reviewed and compared.Results In the group A , there were 13 patients preserved both ovaries , and 7 patients preserved a single ovary.While there were no significant differences in the age, body mass index, surgical staging, histology, grade, cytology of peritoneal lavage or ascites , and postoperative treatment between two groups ( all P>0.05 ).The differences in the level of CA 125 [ 25%(5/20) versus 18%(10/55)] and number of patients underwent pelvic lymphadenectomy [35% (7/20) versus 84%(46/55)] were statistically significant between two groups (all P<0.05).Of seventy-five cases, only two patients relapsed and all survived after a median follow-up time of 31.7 months ( range:0 to 160 months).Kaplan-Meier analysis revealed no difference in overall survival (100.0% versus 100.0%) and disease free survival ( 90.0% versus 95.5%) between two groups ( P =0.579 ).Conclusions Ovarian preservation has no statistically significant impact on the survival of young patients with stage Ⅰa, well differentiated endometrial cancer.Large-scale, prospective clinical studies are needed to validate the safety of ovarian preservation for those patients.

Application of laparoscopy in the modified nerve plane-sparing radical hysterectomy of cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the feasibility and safety of laparoscopic nerve plane-sparing radical hysterectomy (NPSRH) and compare with that of open NPSRH.</p><p><b>METHODS</b>One hundred and thirty-four patients with FIGO stage Ib1-IIa2 cervical cancer were enrolled in the study. Thirty-three patients underwent laparoscopic NPSRH. During the operation, the pelvic autonomic nerve plane which is directly underneath the ureter was integrally preserved by dissecting the pelvic spaces laparoscopically. The vessels around the nerve plane were controlled by Hem-o-lok polymer clips. One hundred and one patients underwent open NPSRH without special instruments. The clinical, pathological and surgery-related parameters were compared between the two groups. Moreover, postoperative short-term bladder function of these patients was also analyzed.</p><p><b>RESULTS</b>There was no significant difference between the laparoscopic group and open group in terms of age, body mass index, previous surgery, FIGO stage, pathologic type, etc. (P > 0.05). The mean duration of surgery in the laparoscopic group was significantly longer [(303.8 ± 67.5) min vs. (272.4 ± 57.5) min] (P < 0.01). But, the laparoscopic group had less blood loss [177.0 ml vs. 474.5 ml, P < 0.01] and blood transfusion rate [ 6.1% (2/33 cases) vs. 49.5% (50/101 cases), P < 0.001]. There was no significant difference regarding the proportion of patients who firstly passed the post-void residual urine volume (PVR) test (P > 0.05). The median time of catheterization between the two groups were also comparable (P > 0.05). However, the postoperative hospital stay was significantly shorter in the laparoscopic group [median postoperative hospital stay 9.2 days vs. 11.0 days, P < 0.001].</p><p><b>CONCLUSIONS</b>Laparoscopic NPSRH is feasible. It seems to be comparable with open NPSRH in terms of preserving pelvic nerve function, but is more favorable in terms of blood loss and postoperative recovery.</p>

Evaluation of pelvic visceral functions after modified nerve-sparing radical hysterectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nerve-sparing radical hysterectomy (NSRH) was developed in an attempt to minimize complications after radical hysterectomy. Since 2008, a modified NSRH-nerve plane-sparing radical hysterectomy (NPSRH) has been developed at the Cancer Hospital, Chinese Academy of Medical Sciences. The aim of this study was to investigate the role of NPSRH in improving postoperative pelvic visceral dysfunctions.</p><p><b>METHODS</b>Eighty-three patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA2 cervical cancer received NPSRH (the study group) from January 2008 to October 2012. One hundred and sixty-six patients who underwent conventional radical hysterectomy (CRH) were randomly selected as the control group. Age, pathological type and stage were matched between the two groups. The safety of surgery was assessed by duration of operation and blood transfusion rate. Postoperative short-term bladder function was analyzed by duration of catheterization. Long-term bladder, anorectal and sexual function were evaluated with questionnaires.</p><p><b>RESULTS</b>Seventy-eight patients (94.0%) in the NPSRH group and one hundred and sixty patients (96.4%) in the CRH group completed the study. Median follow-up time was 31.9 months and 31.0 months respectively (P = 0.708). There was no significant difference between the two groups in terms of age, body mass index, FIGO stage, pathologic type, preoperative and postoperative therapy (P > 0.05). The blood transfusion rate shared no difference between two groups (P = 0.364). The operation time in the NPSRH group was significantly longer than CRH group (P < 0.01). But the duration of catheterization and hospitalization in the NPSRH group was significantly reduced compared with CRH group (P < 0.01). In addition, the incidence of long-term urinary frequency, urinary incontinence, urinary retention, straining to void, constipation and diarrhea was significantly lower in the NPSRH group (P < 0.05). However, there was no significant difference regarding sexual function (P > 0.05).</p><p><b>CONCLUSIONS</b>The current evidence indicated that NPSRH improved long-term bladder function compared to CRH. Moreover, it may improve long-term anorectal function as well.</p>

Clinical analysis of 35 cases of vulvar intraepithelial neoplasia grade Ⅲ / 中华妇产科杂志

Objective To evaluate the etiology, clinicopathological characteristics, treatment and prognosis of VIN Ⅲ. Methods Thirty-five patients with VIN Ⅲ admitted in Cancer Hospital of Chinese Academy of Medical Sciences between 1993 and 2008 were analyzed retrospectively. Results All 35 patients attended to hospital with the symptoms of pruritus vulvae and lumps. Among of them, there were 28 (80%) cases whose lesions presented as multiple plaques, while 7 (20%) eases lesion were monofocal.Fifteen out of 35 eases had coexistent with human papillomavirus (HPV) related lesions, and there were the evidence of HPV in 22 patients whose pathologic sections revealed koilocytes. 34 cases (97%) except one received different types of surgical resections, including wide local resection (14/34), simple vulvectomy (16/34) and simple vulvectomy plus perianal skin resection (4/34), while there two cases shown positive cut-edges and one of them received radiotherapy postoperatively. Four out of the 34 cases recurred locally in 2, 4, 6 and 22 months and received surgical treatment again or laser therapy, respectively. The median follow-up period was 66 months ( range 1-166), and none of them were died of the disease itself except one case died of the concurrent cervical cancer. Among 26 cases received the investigation of the quality of life,there were nine cases (35%) suffered from sexual dysfunction after the operation, and one of them received vulvoplasty. Conclusions VIN Ⅲ has good prognosis. The development of VIN Ⅲ may be related to the infection of HPV, because most of them concurrent with HPV diseases. Its primary treatment is surgical resection, while affecting on the quality of life.

An initial experience of the use of sentinel lymph node biopsy in squamous cell cancer of the vulva / 中华妇产科杂志

Objective To evaluate the feasibility of sentinel lymph node biopsy (SLNB) in patients with vulvar cancer. Methods Twenty-one patients with vulvar squamous cancer undergoing radical surgery admitted in Cancer Hospital of Chinese Academy of Medical Sciences from Oct.2004 to Apr.2008, were enrolled in the study. SLNB procedure was performed with blue dye alone in the first eleven patients, while the later ten patients, a combination procedure with radioactive tracer and blue dye was used to detect sentinel lymph node (SLN). All resected nodes were submitted to the pathological examination, which was considered as the gold standard to determine the efficacy of SLNB. The complications related to SLNB were also observed during the study. Results The sentinel node was identified in 20 patients (95%), included 8 cases with unilateral SLNs and 12 cases with bilateral SLN. A total of 83 SLN were identified with a mean number of 4.2 per patient (range, 1-9) or 2.6 per groin (range, 1-6). Difference between the mean number of SLN (4.4 per patient, 2.5 per groin) identified by blue dye or by combined procedure (3.9 per patient, 2.7 per groin) was not statistically significant (t=0.459,P=0.652;t=-0.421,P=0.717). Twenty patients were detected to positively superficial inguinal SLN and one of them also positively bilateral deep femoral SLN, 8 (10 groins) of them were detected positively nodal metastases. Among of eight patients, 7 (9 groins)of them were detected more than one SLN involved, while 1 of them were detected false-negative node involved. The false negative rate of was 10%(1/10), negative predictive value was 96%(22/23). No complications were attributed to the study. Conclusions SLNB procedure in vulvar cancer is feasible and safe. SLN identification appears to be highly accurate for detecting metastases in the ipsilateral inguinal lymphatic basins.

A prospective study on nerve-sparing radical hysterectomy in patients with cervical cancer / 中华妇产科杂志

Objective To assess the nerve-sparing radical hysterectomy (NSRH) technique and its impact on postoperative voiding function. Methods Forty-fonr patients with International Federation of Gynecology and Obstetrics(FIGO) stage Ⅰ b1 - Ⅱ a cervical cancer were enrolled and randomized into NSRH group ( study group, n = 22) and conventional radical hysterectomy (CRH) group ( control group, n = 22). The pelvic autonomic nerve pathway (including hypogastric nerve, pelvic splanchnic nerve, inferior hypogastric plexus and bladder branch) was completely preserved in the NSRH group. Related parameters were compared between the two groups. Results The estimated blood loss in NSRH group and CRH group were (550±241) ml and (475±284) ml, respectively, with no significant difference (P >0. 05). The mean operation time in NSRH group and CRH group were (329±43) min and (272±56) min, respectively, with a significant difference (P < 0. 01). More patients in NSRH group had post-void residual urine volume (PVR) < 100 ml than that in CRH group on day 8 after surgery (68% vs. 18%, P <0. 01). The median duration of postoperative catheterization was significantly shorter in NRSH group (8 - 23 days, median 8 days) than that in CRH group ( 8 - 32 days, median 20 days; P < 0. 01 ). Neither surgery-related injury nor pathologically positive margin was reported in either of the groups. Conclusions NSRH is a feasible and safe technique for preserving bladder function. Larger prospective studies are needed to confirm the efficacy of this technique.