Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used.

Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected. Median survival after surgery was significantly shorter with complete dLN resection at the time of surgery (49 days (95%CI)) compared to when lymph nodes remained intact (> 88 days; p < 0.05). Survival was partially restored with incomplete lymph node resection and CD8 T cell dependent. Treatment with aCTLA4 whilst effective against the primary tumour was ineffective for metastatic lung disease. Conversely, aPD-1/aCD40 treatment was effective in both the primary and metastatic disease settings and restored the detrimental effects of complete dLN resection on survival. In this pre-clinical lung metastatic disease model that closely reflects the clinical setting, we observe decreased frequency of survival after complete lymphadenectomy, which was ameliorated with partial lymph node removal or with early administration of aPD-1/aCD40 therapy. These findings have direct relevance to surgical lymph node resection and adjuvant immunotherapy in lung cancer, and perhaps other cancer, patients.

[Clinical analysis of 44 cases with malignant transformation of ovarian mature cystic teratoma].

OBJECTIVE: To analyze the clinicopathologic characteristics, treatment and prognostic factors in malignant transformation of mature cystic teratoma (MCT) of ovary. METHODS: The clinical data of 44 patients with MCT from January 1961 to June 2009 were reviewed. RESULTS: The median age of the 44 patients was 48 years (range, 16 - 84 years). Mean tumor size was (16 ± 6) cm. Thirty-two cases were diagnosed squamous cell carcinoma (73%, 32/44), and 5 of them with the elevated level of serumal squamous cell antigen (SCC-Ag). Three of 37 cases (8%, 3/37) were identified with malignant transformation in image examinations. Rapid frozen section examination and multiple-location biopsy were performed in 8 cases, and 5 of them were detected with malignant diseases. Twenty-two patients with disease confined within the unilateral ovary (10 with intact capsule, and 12 with ruptured capsule). Diseases extended extra ovaries in the others 22 patients. The median cumulative overall survivals were 126 and 10 months, respectively. The difference between the two groups was significant (P < 0.01). Twenty-seven patients had no residual tumor after primary surgery. The median cumulative overall survivals between the patients with and without residual tumor were 10 and 84 months respectively, and there were significant difference between two groups (P < 0.01). Seven selected patients with malignant disease confined within unilateral ovary underwent fertility-sparing surgery, and 2 cases of them had successful pregnancies and delivery, while other 4 cases with ruptured capsule recurred. CONCLUSIONS: The most common pathology type of malignant transformation in mature cystic teratoma of the ovary is squamous cell carcinoma. Comprehensive pre-operation image examination and tumor marker level detection might be of great help in diagnosis. Tumor extension extraovary and residual tumor after surgery are the most significant poor prognostic factors. Early stage patient with ruptured capsule should be very discreet to choose fertility-sparing surgery.

Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases.

OBJECTIVE: To discuss the optimal treatment options for stage I patients with endometrial stromal sarcoma (ESS). METHODS: We reviewed hospital records and pathology of 53 patients with ESS at stage I. Statistical analysis was performed using SPSS 12.0 software, and Chi-square test, t-test and log rank test were adopted. RESULTS: Among 53 patients, 37 had low-grade tumors, 11 had undifferentiated endometrial sarcoma (UES) and 5 had unclassified ESS. The median follow-up time was 66 months, and 48 cases were still alive. The overall 2-year and 5-year survival rates were 91.5% and 85.9%, respectively. The recurrence rate of the patients with preserved ovarian function was remarkably higher than that of patients without (100% vs. 22.7%, P<0.001). The patients who received adjuvant whole pelvic radiation (Dt 40 approximately 45 Gy) had obviously higher local control rate than the patients who did not (93.8% vs. 57.1%, P=0.007), but they had similar survival (P=0.963). Among 7 of the 11 UES patients without distant recurrence, 5 received the adjuvant chemotherapy with IAP (ifosfamide 1.0 g, d1-4; epirubicin 25 mg/m2, d1-2; cisplatin 20 mg, d1-5; mensa 0.2 g, 0, 4, 8 h from the application of ifosfamide, d1-4, q 28 days) or VAD (vincristine 1.2 mg/m2, d1; adriamycin 20 mg/m2, d1-3; dacarbazine 250 mg/m2, d1-5, q 28 days), and none of the other 4 cases recurring distantly received the chemotherapy with IAP or VAD. CONCLUSIONS: Surgeries not preserving ovarian function were helpful to decrease the risk of recurrence compared with those surgeries sparing ovarian function. Adjuvant radiotherapy could improve local control but not survival. Adjuvant chemotherapy with IAP or VAD seemed to be beneficial to UES patients.

[Synchronous primary cancers of the endometrium and ovary: review of 43 cases].

OBJECTIVE: To investigate the clinical and pathological characteristics, treatment methods, and prognosis of synchronous primary cancers of the endometrium and ovary. METHODS: The clinical data of 43 patients with synchronous primary cancers of the endometrium and ovary were retrospectively reviewed. The survival was calculated by Kaplan-Meier method and compared using the log-rank test. RESULTS: The median age at diagnosis was 49 years (range, 28-73 years). The most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and enlarged corpus in 27.9% at physical examination, while pelvic masses were found in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in 23.3% (10 cases) during ultrasound examination. Of 25 patients examined by CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All 15 patients who underwent endometrial biopsies were proven to have endometrial carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases; Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases, III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12 patients had pelvic lymph node dissection. Thirty-eight of the 43 patients (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant ovarian histology was endometrioid or mixed tumor with endometrioid components (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had radiation alone and the remaining 4 cases received no adjuvant treatment. The 3- and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3- and 5-year survival rates of patients with both endometrioid and ovarian carcinomas were higher than that of those with non-endometrioid or mixed subtypes (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients with early stage disease were better than those of the other patients (93.3%, 93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was showed by univariate analysis that lower CA125 level, early FIGO stage, and adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5-year survival rates, while only early FIGO stage and chemotherapy plus radiotherapy were revealed by multivariate analysis as independent prognostic factors. CONCLUSION: Synchronous primary cancers of the endometrium and ovary are different from either primary endometrial carcinoma or ovarian cancer, while it can usually be detected in early stage and with a good prognosis. The impact of the CA125 level on prognosis needs to be further studied. Surgical treatment alone may be enough for early stage patients. Chemotherapy plus radiotherapy may be necessary for advanced stage patients.

[Impact of squamous cell carcinoma antigen in patients with recurrent squamous cell carcinoma of the uterine cervix].

OBJECTIVE: To investigate the impact of squamous cell carcinoma antigen (SCCAg) in patients with recurrent squamous cell carcinoma of the uterine cervix. METHODS: Totally 72 patients with recurrent squamous cell carcinoma of the uterine cervix treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, between 1999 and 2005 were retrospectively analyzed to investigate the impact of SCCAg on diagnosis and prognosis by univariate and multivariate analysis. RESULTS: This study included 30 patients with recurrent disease after primary radical surgery and 42 patients with recurrent cervical cancer after radio-chemotherapy. Sixty one patients (85%) had serum SCCAg elevated (>or=1.5 pg/L), and 20 of these (28%) had an increase of SCCAg before clinical manifestation of relapse. The median leading time was 3 months (range: 1-13 months). Forty five patients had no symptoms with only SCCAg elevation, and 15 patients experienced leg edema and (or) sciatic pain, 7 patients suffered from irregular bleeding and 5 patients had symptoms resulting from distant metastasis. Thirty three patients were diagnosed by histology biopsy and (or) cytology, 39 patients were diagnosed with SCCAg elevation and clinical and radiological examinations, 29 of these patients were diagnosed only by SCCAg elevation and CT or MRI. Fourteen patients recurred limited to the cervix or to the cervix and adjacent tissues (central recurrence), 31 cases recurred at pelvis, and 20 patients with distant metastasis and 7 patients suffered from pelvic recurrence and distant metastasis. Twenty three cases received salvage therapy including surgery for patients recurring after definitive radiotherapy and radiotherapy and or conform radiotherapy for patients after primary radical surgery, 46 patients were given palliative chemotherapy and or radiotherapy, and 3 patients refused any treatment. The median and mean survival time were 11 months and 23 months respectively (2-62 months). The 3-year, 5-year overall survival rate were 25% and 19% respectively. Univariate analysis showed SCCAg elevation before primary treatment, grade, recurrent site, treatment method, SCCAg>or=10 pg/L, SCCAg elevation during treatment, and SCCAg not within normal after treatment were correlated with 3-year survival rate. Twenty patients had an increase of SCCAg before clinical manifestation of relapse compared with other patients who did not, and the 3-year survival rate was not significantly different (22% vs 27%). Multivariate analysis revealed that only grade and treatment methods were independent risk factors. CONCLUSION: The impact of the SCCAg in recurrent squamous cell carcinoma of the uterine cervix needs further study.

[Clinical review of 97 patients with endometrial stromal sarcoma].

OBJECTIVE: To review the survival outcomes in patients with endometrial stromal sarcoma (ESS) in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, and to discuss prognostic factors and the role of post-operative adjuvant radiotherapy and chemotherapy. METHODS: Hospital records and pathology reports for 97 patients with ESS were reviewed. Among 97 patients, 69 had low-grade ESS (LGESS), 16 had high-grade ESS (HGESS) and 12 had unclear grade. The median age at diagnosis was 44.0 years. The median follow-up time was 62 months (5 - 277 months). Atypical vaginal bleeding (43%) and prolonged and increased menses (36%) were the main symptoms. RESULTS: Totally 2-year and 5-year cumulative survival rates were 93% and 84%, respectively. Cumulative survival curves were significantly different between LGESS and HGESS, and so did cumulative survival curves between stage I - II and stage III - IV (P < 0.05). Totally, 34 patients (37%) had local or distant recurrence. The median time-to-recurrence (TTR) was 27 months. The recurrence rates of the patients with or without preserve of ovary were 89% and 24%, respectively (P = 0.000). The local-control-rates of the patients who received or did not receive post-operative radiotherapy were 81% and 43%, respectively (P = 0.011). CONCLUSIONS: The prognosis of HGESS is obviously worse than that of LGESS. The risk of recurrence of patients with preserve of ovary was remarkably higher than that of patients without preserve of ovary. Postoperative radiotherapy could increase the local-control-rates.

[Prognostic analysis of 88 patients with ovarian clear cell carcinoma].

OBJECTIVE: To investigate the clinical characteristics of clear cell carcinoma of the ovary and to compare the survival of the patients treated by three different chemotherapy regimens. METHODS: Between 1984 and 2005, the clinical data of 88 surgically treated patients with clear cell carcinoma of the ovary were retrospectively analyzed. Of the 88 patients, 55 (62.5%) had tumor in stage I, 2 in stage II, 22 in stage II, 3 in stage IV and 6 in indefinite stage. These patients underwent either bilateral salpingo-oophorectomy with hysterectomy and omemtectomy or cytoreduction surgery. Of 55 stage I patients, 20 received pelvic lymohadenectomy. All patients were given postoperative chemotherapy, 43 patients received CAP/CP, 33 paclitaxel combination with carboplatinum/cisplatin (TC/TP) and 12 CPT-11 plus MMC. RESULTS: The response rate, recurrence rate, 3- and 5-year survival was 35.0%, 30.2% (13/43), 67.4% (29/43), 43.9% and 29.3%, respectively in patients treated with CAP/CP; 73.9%, 18.2% (6/33), 45.5% (15/33), 57.3% and 40.5%, respectively in the patients with TC/TP; 71.4%, 16.7% (2/12), 25.0% (3/12), 70.7% ( 3-yr survival, no available 5-yr survival), respectively in the patients with CPT-11 + MMC (P < 0.05). During follow-up, 47 (53.4%) patients were found to have recurrence, it was 45.4% (25/55) in stage I patients including 29.6% (8/27) in stage I a + I b and 60.7% (17/28) in stage I c, 75.0% (18/24) in stage II + III and 4/6 in the indefinite FIGO stage. The recurrences rate was 27.8% (5/18) in stage I patients with pelvic lymphadenectomy vs. 51.3% (19/37) in those without. It was 67.3% in 46 patients with elevated CA125, and 38.1% in the other 42 patients with normal or unavailable CA125 (P < 0.05). The overall 3- and 5-year survival rate of 88 patients was 48.7% and 40.9% , respectively, with 72.5% and 66.8% in stage I, 100.0% and 70.5% in stage Ia + Ib, 68.5% and 60.3% in stage Ic, 41.8% and 20.8% in stage II + III, 0 in stage IV (P < 0.05). The 3- and 5-year survival in stage I with pelvic lymphadenectomy was 88.5% and 75.8% vs. 70.3% and 65.1% in those without (P < 0.05). The 3- and 5-year survival of the patients with optimal (residual disease less than 2 cm) was 36.7% and 23.1% vs. 22.2% and 0 in those with suboptimal cytoreduction (P < 0.05), it was 46.8% and 38.8% in the patients with elevated CA125 vs. 46.7% and 43.5% in those with normal one (P > 0.05). CONCLUSION: Our data show that ovarian clear cell cancer patient have a poor response to CAP/CP and may have a better response to TC/TP, especially to CPT-11 plus MMC. However, the overall prognosis is still poor and further clinical investigations are needed to improve it.

[Treatment and prognosis of low-grade malignant endometrial stromal sarcoma].

OBJECTIVE: To review the experience in the treatment of low-grade malignant endometrial stromal sarcoma. METHODS: The data of 41 patients with low-grade malignant endometrial stromal sarcoma surgically treated between 1982 and 2004 were reviewed. Statistical analysis was carried out using chi(2) and Kaplan-Meier life table. RESULTS: Of these 41 patients, 24 suffered from irregular vaginal bleeding, and 30 had been diagnosed to have leiomyoma before treatment. Thirty patients but 11 underwent surgical management with uterus removed. Thirty-three patients received postoperative adjuvant therapy including radiation and/or chemotherapy. The 5-year and 10-year actuarial survival was 87. 5% and 77. 8%, respectively. Eighteen patients (43. 9%) developed recurrent disease, most of which in the pelvis. The mean time to recurrence was 31 months (range 6 to 78 months) with the median time of 26 months. The recurrent rate was 66.7% for patients whose ovarian function was reserved versus 37. 5% for those without reservation. Patients who received adjuvant therapy had a lower recurrent rate (30. 3%) than those who did not (87. 5%). The recurrent rate of the patients treated with postoperative adjuvant radiation was 32. 3% (10/31) versus 80% (8/10) for those patients without. The 5-year actuarial survival rate of patients with recurrent disease was 71. 8%. CONCLUSION: Low-grade malignant endometrial stromal sarcoma has a good prognoses though dwarfed by higher late recurrence after initial treatment. Postoperative adjuvant radiation is helpful to reduce local recurrence. Endometrial stromal sarcoma;

[Efficiency and side effects of concurrent radiotherapy and chemotherapy for advanced cervical cancers].

OBJECTIVE: To investigate the efficiency of concurrent radiotherapy and chemotherapy for advanced cervical cancer. METHODS: Between Dec. 1999 and Dec. 2003, 158 women with cervical cancer were treated with concurrent radiotherapy and chemotherapy. The regimen was 45 Gy/25 fraction radiation to the pelvis, intracavitary after-loading 7-9 fractions, (42 +/- 7) Gy to point A and 10-30 Gy to cervical submucosa 0.5 cm for debulking; meanwhile, chemotherapy was given with cisplatin 60 mg/m2, d1-d4, and 5-Fu 2400 mg/m2, over a 96-hour period. RESULTS: The rate of local resistence and pelvic recurrence was 4.4% and 3.2%, respectively. The rate of distant metastasis was 17.1%. The overall 5-year survival rate was 66.3%, without statistically significant difference between concurrent chemoradiation group and radiation alone group during the same period. The adverse effect included grade 3 or grade 4 leukopenia in 12.7% of these patients, grade 3 thrombocytopenia in 1.3%, anemia in 3.2%, diarrhoea in 17.8%, cardiac toxicity in 10.1% and radiation- related rectitis in 13.3% and cystitis in 0.6%, but alopecia was rare. CONCLUSION: Concurrent chemotherapy and radiotherapy may not be able to improve survival for advanced cervical cancer, however, adverse effect is tolerable.

[Border-line smooth-muscle tumor of the uterus: analysis of 131 patients].

OBJECTIVE: To investigate whether the border-line uterine smooth-muscle tumor is different from leiomyoma or leiomyosarcoma in history and clinical manifestations. METHODS: The medical records of 131 surgically treated patients suffering from the so-called cellular leiomyoma or mitotically active leiomyoma of the uterus treated from 1984 to 2002 were retrospectively reviewed. All pathological sections of these patients were reviewed by a senior pathologist. Chi-square test and Kaplan-Meier life table were used for statistical analysis. RESULTS: The overall 5-year survival rate of patients with the border-line uterine smooth-muscle tumors was 100%, however, 19.1% (24/131) of whom developed a late recurrence and 8 patients had repeated recurrences with a more shortened course and aggressive potential changes of mitosis and cellular atypia. The overall 5-year survival rate the patients with recurrence was 91.7%, but only 75.0% for those with repeated recurrences. CONCLUSION: Patients with border-line uterine smooth-muscle tumor do possess some difference in nature from the leiomyoma or leimyosarcoma. Long-term follow-up is very important for these patients after surgery.

[Clinical analysis of 11 cases of ovarian Setoli-Leydig cell tumor].

OBJECTIVE: To study the clinical characteristics, treatment and prognostic factors of ovarian Setoli-Leydig cell tumor. METHODS: During 1962 - 2002, a total of 11 patients with Setoli-Leydig cell tumor were retrospectively analyzed. RESULTS: Microscopically, seven of the neoplasms were well differentiated, 3 were moderately differentiated and 1 was poorly differentiated. Nine of the tumors were stage Ia, 1 was stage IIc and 1 was stage IIIc. The most frequent symptoms were abdominal-pelvic masses. Six patients presented with androgenization and virilization, 3 of which had their serum testosterone tested, and the levels were elevated. Five patients presented with metromenorrhagia and abnormal vaginal bleeding. One of them was both androgenized and estrogenized. In addition, five patients had diseases associated with excessive estrogenic stimulation, such as uterine myoma and endometrial hyperplasia. Two patients suffered from breast cancer. All patients were subjected to operation. And 5 patients with poorly differentiated or stage II-III tumors were subjected to postoperational chemotherapy. After 6 months to 34 years follow-up, no patient died of this disease. Three patients who received conservative surgery achieved normal menstruation 1 - 3 months after operation, and one of them gave birth to a child. CONCLUSIONS: Ovarian Setoli-Leydig cell tumor has good prognosis. Surgery alone is a currently acceptable treatment for patients with well-differentiated early stage tumors. For patients with poorly differentiated or advanced tumors, postoperational chemotherapy seems to be necessary. Conservative surgery should be the treatment of choice in young patients who need future fertility.

[Effects of tillage mode and nitrogen application rate on nitrogen use efficiency of wheat in a farming-pasture zone of North China].

A field experiment was conducted in a farming-pasture zone in Chifeng City of Inner Mongolia Autonomous Region, North China to investigate the effects of different tillage modes and nitrogen (N) application rates on the grain yield and nitrogen use efficiency (NUE) of winter wheat. The results showed that long term conservation tillage increased the wheat NUE by 3% -4%, and decreased the environmental pollution by fertilizer N. Conservation tillage promoted the N absorption by wheat, and increased the grain yield. When the N application rate increased from 120 kg hm-2 to 360 kg . hm-2, the NUE decreased from 36. 5% to 26% , fertilizer N loss increased by about 5% , i. e. , the corresponding N loss was increased from 60 kg hm-2 to 200 kg hm-2, and the environmental N pollution increased markedly. The wheat NUE of the residual N in last season was less affected by tillage mode, but more affected by the N application rate in last season, with an overall tendency of the higher the N application rate in last season, the lower the NUE and the more the fertilizer N loss. After two seasons' wheat planting, the proportion of the total nitrogen recovery by the wheat-soil system was about 44% -50%, among which, the residual N in soil occupied about 13% -18% of applied N.

[Multivariate analysis of prognostic factors in endometrial carcinoma].

BACKGROUND & OBJECTIVE: A number of prognostic factors have been evaluated in endometrial carcinoma. Among them, only a few factors have been recognized as major adverse factors affecting prognosis independently. This study was to explore the independent prognostic factors in endometrial carcinoma. METHODS: A total of 265 patients who accepted primary surgical treatment in our hospital from Jan. 1990 to Dec. 2000 were studied retrospectively. Prognostic factors were analyzed using univariate model and multivariate regression model. RESULTS: The 5-year recurrence-free survival rate of all patients was 83.3%, and 5-year overall survival rate was 84.3%. The univariate model revealed that clinical stage, pathological stage, pathologic grade, pathologic subtype, depth of muscularis invasion, cervical invasion, lymph node metastasis, peritoneal cytology, lymph-vascular invasion, and adnexa metastasis significantly associated with 5-year recurrence-free survival, and 5-year overall survival (P< 0.05), while age, and complications have no significant association with prognosis (P >0.05). However,on multivariate regression analysis, only pathohistological stage, pathologic grade, depth of muscularis invasion, and cervical invasion significantly correlated with 5-year recurrence-free survival, and 5-year overall survival (P< 0.05); clinical stage correlated with 5-year recurrence-free survival significantly (P< 0.001), but not with 5-year overall survival (P=0.074). Hematogenous dissemination rate of patients with muscularis invasion of >50% was significantly higher than that with muscularis invasion of