Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. @*Materials and Methods@#TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. @*Results@#The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. @*Conclusion@#Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

A prospective study comparing endoscopic subcutaneous mastectomy plus immediate reconstruction with implants and breast conserving surgery for breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Breast conserving surgery (BCS) has been the standard surgical procedure for the treatment of early breast cancer. Endoscopic subcutaneous mastectomy (ESM) plus immediate reconstruction with implants is an emerging procedure. The objective of this prospective study was to evaluate the clinical outcomes of these two surgical procedures in our clinical setting.</p><p><b>METHODS</b>From March 2004 to October 2007, 43 patients with breast cancer underwent ESM plus axillary lymph node dissection and immediate reconstruction with implants, while 54 patients underwent BCS. The clinical and pathological characteristics, surgical safety, and therapeutic effects were compared between the two groups.</p><p><b>RESULTS</b>There were no significant differences in the age, clinical stage, histopathologic type of tumor, operative blood loss, postoperative drainage time, and postoperative complications between the two groups (P > 0.05). The postoperative complications were partial necrosis of the nipple and superficial skin flap in the ESM patients, and hydrops in the axilla and residual cavity in the BCS patients. There was no significant difference in the rate of satisfactory postoperative cosmetic outcomes between the ESM (88.4%, 38/43) and BCS (92.6%, 50/54) patients (P > 0.05). During follow-up of 6 months to 4 years, all patients treated with ESM were disease-free, but 3 patients who underwent BCS had metastasis or recurrence -one of these patients died of multiple organ metastasis.</p><p><b>CONCLUSIONS</b>After considering the wide indications for use, high surgical safety, and favorable cosmetic outcomes, we conclude that ESM plus axillary lymph node dissection and immediate reconstruction with implants - the new surgery of choice for breast cancer - warrants serious consideration as the prospective next standard surgical procedure.</p>

FDG PET/CT versus PET alone for pre-surgical detection of lymph node metastasis in esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the combined FDG PET/CT with PET alone in the detection of lymph node metastasis (LNM) for esophageal carcinoma patient.</p><p><b>METHODS</b>From November 2003 to August 2005, 35 patients with esophageal carcinoma underwent FDG PET/CT before esophagectomy and lymph node (LN) dissection. The patients who had history of previous anticancer treatment or diabetes mellitus and inflammatory lung diseases as well as being inoperable for medical reasons were excluded. The results of LNM detection by PET/CT and PET alone were compared with pathological results.</p><p><b>RESULTS</b>Twenty-nine men and 6 women were eligible for this study, with a mean age of 57 years (range: 40 to 72 years). Of these 35 patients, 3 had lesion at the upper third thoracic esophagus, 22 at the middle third and 10 at the lower third. All patients underwent surgical resection successfully. Twenty-five patients and 65 out of 313 excised nodal groups were found to have metastases by pathological examination. The true positive and true negative LNM interpretation reached 61 and 229 LN groups on PET/CT versus 53 and 217 LN groups on PET alone. False negative LNM interpretation was found in 12 LN groups on PET alone, and 8 of them were corrected by PET/CT including one cervical LN, 4 paraesophageal LNs, one left gastric arterial LN, one left gastric cardia LN, one lesser gastric curve LN. False positive interpretations on PET alone were found in 31 LN groups, 12 of them were corrected by PET/CT which included 9 false-positive interpretations due to physical tracer uptake (2 in the cervical region and 7 in gastrointestinal tract ) and 3 lesions with heterogeneous tracer uptake in the primary tumor. The sensitivity, specificity and accuracy of LNM detection by PET alone was 81.54% (53/65), 87.50% (217/248), and 86.26% (270/313), whereas by PET/CT, which was 93.85% (61/65), 91.24% (229/248) and 92.65% (290/313), respectively. There were statistically significant differences in sensitivity and accuracy of LNM detection between PET/CT and PET alone (0.033 and 0.009).</p><p><b>CONCLUSION</b>Compared with FDG PET alone, FDG PET combined with CT can improve the sensitivity and accuracy in detection of lymph node metastasis in esophageal carcinoma.</p>

Contribution of minute axillary lymph nodes to accurate staging for patients with breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Axillary lymph node metastasis is a very important metastatic pathway in breast cancer and its accurate detection is important for staging tumour and guiding therapy. However, neither the accuracy of routine detection of lymph node in surgical specimens nor the significance of minute lymph node with metastases in breast cancer is clear. A modified method for conveniently detecting minute lymph node in specimens of axillary dissections in patients with breast cancer was used to analyze their influence on staging breast cancer.</p><p><b>METHODS</b>Lymph nodes in fresh, unfixed, specimens of axillary dissections from 127 cases of breast cancer were detected routinely. Then the axillary fatty tissues were cut into 1 cm thick pieces, soaked in Carnoy's solution for 6 to 12 hours, taken out and put on a glass plate. Minute lymph nodes were detected by light of bottom lamp and examined by routine pathology.</p><p><b>RESULTS</b>Lymph nodes (n = 2483, 19.6 +/- 8.0 per case) were found by routine method. A further 879 lymph nodes up to 6 mm (781 < 3 mm, 6.9 +/- 5.3 per case, increasing mean to 26.5 +/- 9.7) were found from the axillary tissues after soaking in Carnoy's solution. By detection of minute lymph nodes, the stages of lymph node metastasis in 7 cases were changed from pathological node (pN) stage pN(0) to pN(1) in 4 cases, from pN(1) to pN(2) in 2 and from pN(2) to pN(3) in 1.</p><p><b>CONCLUSIONS</b>The accurate staging of axillary lymph node metastasis can be obtained routinely with number of axillary lymph nodes in most cases of breast cancer. To avoid neglecting minute lymph nodes with metastases, small axillary nodes should be searched carefully in the cases of earlier breast cancer with no swollen axillary nodes. Treatment with Carnoy's solution can expediently detect minute axillary nodes and improve the accurate staging of lymph nodes in breast cancer.</p>

Technique investigation of endoscopic axillary lymph node dissection by liposuction / 中华外科杂志

<p><b>OBJECTIVE</b>To study the technique of endoscopic axillary lymph node dissection by liposuction.</p><p><b>METHODS</b>Endoscopic axillary lymph node dissection (E-ALND) after liposuction (group A) were performed on 45 patients with breast cancer from Dec. 2004 to Oct. 2005. It was compared with traditional ALND (group B).</p><p><b>RESULTS</b>The average operation time of E-ALND was 108 min (60 - 190 min), it was longer than that in group B (P < 0.05). The total blood loss in group A was 152.82 ml (80 - 220 ml), it was less than that in group B significantly (P < 0.01). In group A, the mean lymph nodes harvested by endoscopy were 18 (8 - 34), the total postoperative lymph flow was 140.38 ml (60 - 180 ml), the duration of drainage was 6.91 d (6 - 15 d). The postoperation complication included axillary seromas 7 cases, epidermic blister 5 cases, operation area phlegmon 2 cases were found in group A. There was no significant difference between two groups in the total postoperative lymph flow, the duration of drainage and the number of dissected lymph nodes and postoperation complication. The incision of chest wall was smaller in group A, and patients by this surgery were satisfied with the cosmetic results.</p><p><b>CONCLUSIONS</b>Endoscopic axillary lymph node dissection by liposuction could match the traditional lymphadenectomy. The technique should be further standardized.</p>

Value of ~(18)FDG PET-CT in defining the length of esophageal cancer / 中华放射肿瘤学杂志

Objective To assess the value of 18-fluoro-deoxy-glucose positron emission-CT(FDG PET-CT) in defining the length of primary esophageal cancer.Methods Thirty-two patients had underg- one esophagoscopy,esophagography and FDG PET-CT scans one week before esophagectomy.There was one tumor located in the upper thoracic esophagus,22 in the middle thoracic esophagus,and 9 in the lower tho- racic esophagus.The location and length of primary lesion of the tumor was determined by esophagoscopy, esophagography,and FDG PET-CT.The length of the abnormality seen on the CT portion of the PET-CT scan was determined separately and independently by two radiologists.All results were compared with the resected specimen.Results According to esophagography,CT and PET-CT,all lesion lengths were compared with that of the resected specimen.It was found that the tumor location determined by esophagoscopy was not in accordance with the resected specimen in 2 patients.The mean length of the primary tumor,being from short to long,were (3.8?1.4),(4.1?1.5),(4.4?1.6),(5.3?1.9) and (4.7?1.7) cm,as determined by esophagoscopy,esophagography,CT,actral length of the resected specimen and PET-CT.Compared with the resected specimen,there was obvious difference (P=0.000,0.007,0.025,0.001).Considering that there might be some kind of shrinkage in the resected specimen (about 83.59%,as reported by Ma et al), we rectified the length of resected specimen and compared with other findings again.It was found that insig- nificant difference existed between PET-CT and rectified length value of the resected specimen (P=0.082). Conclusions FDG PET-CT is effective in the length determination of primary esophageal cancer.It may he used to determine the length of esophagus to be resected for patients indicated for esophagectomy.It may also be used to ac- curately delineate the gross tumor volume for patients eligible for radiotherapy.

Characteristic and Clinicopathologic Significance of Microlymphatic Vessel in Breast Cancer / 中国普外基础与临床杂志

Objective To investigate the characteristics and clinicopathologic significance of microlymphatic vessel in breast cancer.Methods The microlymphatic density(MLD)and lymphatic vessel invasion(LVI)in 102 cases of breast cancer tissue were evaluated by immunohistochemical staining,using monoclonal antibody for podo- planin.The characteristic of microlymphatic vessel and the relationship between MLD,LVI and clinicopathological parameters were evaluated.And blood vessels were also detected with CD34 by double-labeling immunohistochemis- try for confirming the specificity of podoplanin for microlymphatic vascular.Results Podoplanin antibody was spe- cific for lymphatic vessel without intersection with blood vessel.The density and morphology of microlymphatic ves- sel in breast cancer had significant heterogeneity.The MLD in breast cancer tissues was significantly higher than that in normal breast tissues.The microlymphatic vessel that in breast cancer tissues indicated by a more irregular shape and a larger open lumen,and some cancer embolus entering the open microlymphatic vessel could be seen. MLD was significantly correlated with LVI(P