Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma / 中华肿瘤杂志

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.

Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma / 中华肿瘤杂志

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

Endometrioid adenocarcinoma with proliferated stromal cells, hyalinization and cord-like formations: A case report / 北京大学学报(医学版)

Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.

Clinicopathological features of Helicobacter pylori-negative early gastric cancer / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer.@*METHODS@#The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore.@*RESULTS@#The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp.@*CONCLUSION@#Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

Skip metastasis at the esophageal resection margin in radical gastrectomy: clinical characteristics of 30 cases / 中华胃肠外科杂志

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.

Feasibility of a single-port thoracoscopy-assisted five-step laparoscopic procedure via transabdominal diaphragmatic approach for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma / 中华胃肠外科杂志

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.

Clinicopathological analysis of primary gastric (gastrointestinal)-type mucoglandular lesion of endometrium / 中华病理学杂志

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations / 中华病理学杂志

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

Growth Regularity of Pulmonary Ground Glass Nodules Based on 3D Reconstruction Technology / 中国肺癌杂志

BACKGROUND@#Since the popularization of computed tomography (CT) technology, the detection rate of pulmonary ground glass nodules (GGNs) with imaging follow-up as the main management method has increased significantly. The purpose of this study is to quantitatively analyze the changes of pulmonary GGNs during the follow-up process with three-dimensional reconstruction technology, explore the natural progression of pulmonary GGNs, and provide effective basis for clinical guidance for patients to conduct reasonable management of nodules.@*METHODS@#A total of 115 cases of pulmonary GGNs with regular follow-up in the Combined Outpatient Department of Zhoushan Hospital from March 2015 to November 2022 were enrolled. Quantitative imaging features of nodules were extracted by semi-automatic segmentation of 3D Slicer software to evaluate the growth of nodules and clinical intervention during follow-up.@*RESULTS@#The average baseline age of the patients was (56.9±10.1) yr. The mean follow-up time was (48.8±18.9) months. The two-dimensional diameter of baseline CT scan was (7.9±2.9) mm, and the maximum three-dimensional diameter was (10.1±3.4) mm. The two-dimensional diameter of the last CT scan was (9.9±4.7) mm, and the maximum three-dimensional diameter was (11.4±5.1) mm. A total of 27 cases (23.5%) showed an increase during follow-up, with a median volume doubling time of 822 days and a median mass doubling time of 1,007 days. 32 cases were surgically resected, including 6 cases of invasive adenocarcinoma (IAC), 16 cases of minimally invasive adenocarcinoma (MIA), 8 cases of adenocarcinoma in situ (AIS) and 2 cases of atypical adenomatous hyperplasia (AAH). Five nodules underwent surgical intervention due to the progression of two-dimensional diameter, which was pathologically confirmed as pre-invasive lesions, but their three-dimensional maximum diameter showed no significant change. Nodular morphology, lobulated sign, spiculated sign and vacuole signs all promoted the growth of nodules in univariate analysis. There were significant differences in age, baseline diameter, mean CT value, median CT value, 10% and 90% percentile CT number between the growth group and the stable group (P<0.05). Multivariate Logistic regression analysis showed that age and average CT value were risk factors for nodule growth (P<0.05). Receiver-operating characteristic (ROC) curve analysis results indicated that the age ≥63 years old, the baseline three-dimensional maximum diameter ≥9.2 mm, and the average CT value ≥-507.8 HU were more likely to accelerate the growth of GGNs. The maximum three-dimensional diameter ≥14.4 mm and the average CT value ≥-495.7 HU may be a higher malignant probability.@*CONCLUSIONS@#GGNs show an inert growth process, and the use of three-dimensional measurements during follow-up is of greater significance. For persistent glass grinding nodules ≥63 years old, the baseline three-dimensional maximum diameter ≥9.2 mm, and the average CT value ≥-507.8 HU are more likely to increase. However, most nodules still have good prognosis after progression, and long-term follow-up is safe.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma / 中国医学科学院学报

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

From left to right. para-aortic lymph nodes sampling during pancreatoduodenectomy for pancreatic cancer / Da esquerda para a direita. ressecção de linfonodos para-aórticos durante duodenopancreatectomia para câncer pancreático

ABSTRACT BACKGROUND: Para-aortic lymph nodes involvement in pancreatic head cancer has been described as an independent adverse prognostic factor. To avoid futile pancreatic resection, we systematically perform para-aortic lymphadenectomy as a first step. AIMS: To describe our technique for para-aortic lymphadenectomy. METHODS: A 77-year-old female patient, with jaundice and resectable pancreatic head adenocarcinoma, underwent pancreaticoduodenectomy associated with infracolic lymphadenectomy. RESULTS: The infracolic anterior technique has two main advantages. It is faster and prevents the formation of postoperative adhesions, which can make subsequent surgical interventions more difficult. CONCLUSIONS: We recommend systematic para-aortic lymphadenectomy as the first step of pancreaticoduodenectomy for pancreatic head adenocarcinoma by this approach.

RESUMO RACIONAL: O envolvimento dos gânglios linfáticos para-aórticos no câncer da cabeça do pâncreas tem sido descrito como um fator prognóstico adverso independente. Para evitar a ressecção pancreática inútil, realizamos sistematicamente linfadenectomia para-aórtica. OBJETIVOS: Descrever a técnica de linfadenectomia para-aórtica. MÉTODOS: Paciente do sexo feminino, 77 anos, com quadro de icterícia e adenocarcinoma da cabeça do pâncreas ressecável, submetida à duodenopancreatectomia associada à linfadenectomia infracólica. RESULTADOS: Esta técnica anterior infracólica tem duas vantagens principais: é mais rápida e evita a formação de aderências pós-operatórias, o que pode dificultar as intervenções cirúrgicas subsequentes. CONCLUSÕES: Recomendamos a linfadenectomia para-aórtica sistemática como o primeiro passo da duodenopancreatectomia para o adenocarcinoma da cabeça do pâncreas por esta abordagem.

Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Persistent increase and improved survival of stage I lung cancer based on a large-scale real-world sample of 26,226 cases / 中华医学杂志(英文版)

BACKGROUND@#Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes.@*METHODS@#Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method.@*RESULTS@#A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports.@*CONCLUSIONS@#Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.

Short-term outcomes and long-term quality of life after undergoing radical proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis for Siewert type II and III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis / 中华胃肠外科杂志

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ2=8.711, P=0.003 and χ2=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ2=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ2=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.

Advances in the Study of Invasive Non-mucinous Adenocarcinoma with Different Pathological Subtypes / 中国肺癌杂志

Lung cancer is the leading cause of cancer death in the world today, and adenocarcinoma is the most common histopathological type of lung cancer. In May 2021, World Health Organization (WHO) released the 5th edition of the WHO classification of thoracic tumors, which classifies invasive non-mucinous adenocarcinoma (INMA) into lepidic adenocarcinoma, acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma, and micropapillary adenocarcinoma based on its histological characteristics. These five pathological subtypes differ in clinical features, treatment and prognosis. A complete understanding of the characteristics of these subtypes is essential for the clinical diagnosis, treatment options, and prognosis predictions of patients with lung adenocarcinoma, including recurrence and progression. This article will review the grading system, morphology, imaging prediction, lymph node metastasis, surgery, chemotherapy, targeted therapy and immunotherapy of different pathological subtypes of INMA.
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Clinical Study of Artificial Intelligence-assisted Diagnosis System in Predicting the Invasive Subtypes of Early-stage Lung Adenocarcinoma Appearing as Pulmonary Nodules / 中国肺癌杂志

BACKGROUND@#Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules.@*METHODS@#Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed.@*RESULTS@#In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively.@*CONCLUSIONS@#Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.

Related factors of postoperative complications of radical resection for adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

Adenocarcinoma of esophagogastric junction (AEG) is at a special anatomic site with obviously higher morbidity of postoperative complication than gastric cancers at other sites. Postoperative quality of life and survival rate are influenced by the occurrence of complications. Moreover, the perioperative complications are associated with multiple factors such as patient factors (advanced age, obesity and preoperative nutritional status), surgical factors (surgical route, surgical procedure, resection range and prophylactic multivisceral resection), tumor factors (size, stage) etc. Optimizing perioperative management and formulating standardized surgical methods are the key points to prevent postoperative complications of AEG. In conclusion, we should strive to ensure the radical resection and reduce the occurrence of postoperative complications in order to truly benefit patients.

Treatment of Siewert type II adenocarcinoma of the esophagogastric junction: the perspectives from thoracic surgery / 中华胃肠外科杂志

A greater controversy remains in clinical diagnosis and treatment of Siewert type II adenocarcinoma of esophagogastric junction (AEG), compared with Siewert type I and III AEG. In 2018, the first edition of Chinese Expert Consensus on the Surgical Treatment for Adenocarcinoma of Esophagogastric Junction was published in the Chinese Journal of Gastrointestinal Surgery. In the past few years, the advance in minimally invasive thoracoscopic surgery has been proven to reduce thoracic trauma in Siewert type II AEG. Meanwhile, distal thoracic esophagectomy can achieve more complete resection, and upper abdomen-right thoracic approach can ensure the mediastinal lymph node dissection and improve long-term survival. The concept and practice of endoscopic surgery and the comprehensive treatment also give new supplements to the treatment regimen of Siewert type II AEG. More clinical researches should be conducted to address the surgical residual safety and lymph node dissection issues.

Standardized implementation of minimally invasive surgery for Siewert Ⅱ esophagogastric junction adenocarcinoma / 中华胃肠外科杂志

The incidence of Siewert type II adenocarcinoma of the esophagogastric junction (AEG) is increasing year by year. Due to its special anatomical location and biological behavior, the treatment of AEG is still controversial in terms of lymph node dissection, the esophageal resection margin, range of gastrectomy, and the choice of reconstruction modality for postoperative gastrointestinal tract. The advent of the minimally invasive era has brought the treatment of Siewert type II AEG to a stage of gradual improvement and standardization. Experts of China are also actively exploring the value of minimally invasive surgery in the treatment of AEG through multicenter trials (CLASS-10, etc.). It is believed that based on the active development of many clinical studies, basic experimental studies and large prospective clinical studies, the strengthening of communication and cooperation among various disciplines and the innovative application of new technologies can bring greater survival benefits to patients.