Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Pelvic Exenteration ; Biological Products/therapeutic use* ; Pelvic Floor/pathology* ; Neoplasm Recurrence, Local/surgery* ; Rectal Neoplasms/surgery* ; Postoperative Complications/prevention & control* ; Retrospective Studies ; Treatment Outcome

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Humans ; Adult ; Retrospective Studies ; Neoplasm Recurrence, Local ; Hematologic Neoplasms/therapy* ; Busulfan/therapeutic use* ; Graft vs Host Disease/prevention & control* ; Chronic Disease ; Unrelated Donors ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Transplantation Conditioning

OBJECTIVE: To analyze the survival, prognostic factors, and prevention of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies, and explore the relationship between immune reconstruction, loss of human leukocyte antigen (HLA-loss) and relapse after transplantation. METHODS: From July 2012 to June 2020, 47 patients with hematological malignancies who relapsed after allo-HSCT were retrospectively analyzed, including 20 cases undergoing matched-sibling donor transplantation (MSD), 26 cases undergoing haploidentical transplantation (HID), and 1 case undergoing matched-unrelated donor transplantation (MUD). Multivariate analysis was used to analyze the risk factors related to post-relapse overall survival (PROS). RESULTS: All the 47 patients were implanted successfully. The cumulative incidence of grade Ⅱ-Ⅳ, Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 40.4%, 10.6%, and 31.9%, respectively. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in HID group was 42.3% and 11.5%, while in MD group was 38.1% and 9.5% (P=0.579, P=1.000), and the incidence of cGVHD in the two groups was 34.6% and 28.6% (P=0.659). The PROS of patients with NK cell absolute count > 190 cells/μl 30 days after transplantation was higher than that of patients with NK cell absolute count ≤190 cells/μl (P=0.021). The 1-year and 3-year PROS of all the patients was 68.1% and 28.4%, respectively, while in the HID group was 78.9% and 40.3%, in the MD group was 54.4% and 14% (P=0.048). Multivariate analysis showed that grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months were independent risk factors of PROS (P<0.05). CONCLUSION The therapeutic effect of haploidentical transplantation in patients with relapsed hematological malignancies after allo-HSCT is better than that of matched donor transplantation. The high absolute count of NK cells 30 days after transplantation can increase PROS. Grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months have prognostic significance for long-term survival of patients with relapsed hematological malignancies after transplantation.
Graft vs Host Disease/prevention & control* ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; Siblings

Objective: Peripheral T-cell lymphomas (PTCLs) confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to its rarity and heterogeneity. The purpose was to review key points of allo-HSCT for PTCLs, including indication, times of transplantation, conditioning regimen, graft versus host disease prophylaxis, and treatment of relapse. Data Sources: A comprehensive search in PubMed and Cochrane up to February 28, 2018, with the keywords "Peripheral", "T", "Lymphoma", and "Transplantation" was done. Study Selection: Relevant articles including HSCT for PTCLs were carefully reviewed. Results: Promising data have been reported from advances in transplant technology and more and more PTCLs patients with poor prognosis could benefit from allo-HSCT. Conclusion Allo-HSCT is a useful choice for patients with refractory/relapsed PTCLs or high-risk new diagnosed PTCLs.
Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, T-Cell, Peripheral ; therapy ; Neoplasm Recurrence, Local ; Transplantation Conditioning ; Transplantation, Homologous

OBJECTIVETo examine the association of preoperative carcinoembryonic antigen (CEA) level with the efficacy of neoadjuvant radiochemotherapy and postoperative metastasis and relapse in patients with rectal cancer.

METHODSBetween January 2011 and January 2014, 325 patients with local advanced rectal cancer underwent preoperative radiochemotherapy and radical operation in Department of Colorectal Cancer Surgery, Beijing University Cancer Hospital, including 194 males and 131 females. According to preoperative MRI, all the patients suffered from clinical T3-4 tumors or positive lymph nodes. Their Zubrod-ECOG-WHO score was 0-1. These patients received preoperative intensity modulated radiotherapy which consisted of 50.6 Gy in 22 fractions (IMRT GTV 50.6 Gy/CTV 41.8 Gy/22 f) with capecitabine(825 mg/m, twice per day) as radiosensitizer. According to the preoperative serum CEA level, patients were divided into high group (125 cases) and normal group (200 cases). In high group, serum CEA level decreased into normal range in 60 patients (high-normal group) after radiochemotherapy, while it was still in high level in other 65 patients (high-high group). The differences in sensitivity to radiochemotherapy and 3-year disease free survival (DFS) of these patients were both evaluated.

RESULTSIn high group and normal group, the complete response rates were 18.4% (23/125) and 17.5% (35/200) (χ=0.319, P=0.660); the percentages of tumor regression grade(TRG) 0-1 patients were 68.0%(85/125) and 67.5%(135/200)(χ=0.009, P=0.925); the T downstage rates were 63.2%(79/125) and 70.0%(140/200)(χ=1.266, P=0.274), respectively, whose differences were all not significant. The 3-year DFS rate in high group was 62.4%, which was significantly lower than 93.5% in normal group (χ=53.147, P=0.000). There were 65 patients in high-high group, accounting for 52% (65/125) of high group. Among these 65 patients, 44(67.7%) presented recurrence and metastasis within 3 years and the 3-year DFS was 32.3%, which was much lower than 95.0% of 60 patients in high-normal group(χ=182.085, P=0.000).

CONCLUSIONSPreoperative serum CEA level may not be used to predict tumor response of rectal cancer patients who receive preoperative radiochemotherapy. However, the prognosis of patients with high CEA level is worse. Recurrence and metastasis are more likely to occur in patients with high CEA level after radiochemotherapy.

Adult ; Aged ; Biomarkers, Tumor ; blood ; Carcinoembryonic Antigen ; blood ; Chemoradiotherapy ; statistics & numerical data ; Digestive System Surgical Procedures ; statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; statistics & numerical data ; Neoplasm Metastasis ; prevention & control ; Neoplasm Recurrence, Local ; prevention & control ; Predictive Value of Tests ; Prognosis ; Rectal Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

OBJECTIVETo investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT).

METHODFrom March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years.

RESULTSA total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%.

CONCLUSIONSOrgan preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.

Adult ; Aged ; Anal Canal ; surgery ; Biopsy ; Chemoradiotherapy ; Digestive System Surgical Procedures ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; secondary ; surgery ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; prevention & control ; Organ Preservation ; Quality of Life ; Rectal Neoplasms ; mortality ; surgery ; therapy ; Reoperation ; Salvage Therapy ; Survival Rate ; Treatment Outcome ; Watchful Waiting ; methods

Lateral pelvic lymph node metastasis is an important metastatic mode and a major cause of locoregional recurrence of mid-low rectal cancer. Recently, there is an East-West discrepancy in regard to the diagnosis, clinical significance, treatment and prognosis of lateral pelvic lymph node metastasis. In the West, lateral nodal involvement may represent systemic disease and preoperative chemoradiotherapy can sterilize clinically suspected lateral nodes. Thus, in many Western countries, the standard therapy for lower rectal cancer is total mesorectal excision with chemoradiotherapy, and pelvic sidewall dissection is rarely performed. In the East, and Japan in particular, however, there is a positive attitude in regard to lateral pelvic lymph node dissection (LPND). They consider that lateral pelvic lymph node metastasis is as regional metastasis, and the clinically suspected lateral nodes can not be removed by neoadjuvant chemoradiotherapy. The selective LPND after neoadjuvant chemoradiotherapy may be found to be promising treatment for the improvement of therapeutic benefits in these patients. Therefore, the large-scale prospective studies are urgently required to improve selection criteria for LPND and neoadjuvant treatment to prevent overtreatment in the near future. Selective LPND after neoadjuvant treatment based on modern imaging techniques is expected to reduce locoregional recurrence and improve long-term survival in patients with mid-low rectal cancer.
Chemoradiotherapy ; Digestive System Surgical Procedures ; trends ; Humans ; Lymph Node Excision ; methods ; trends ; Lymphatic Metastasis ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; prevention & control ; Pelvis ; surgery ; Prognosis ; Rectal Neoplasms ; surgery ; therapy

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC.
Adenocarcinoma, Clear Cell/drug therapy/*etiology/metabolism ; Antineoplastic Agents/therapeutic use ; Female ; Forecasting ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Ovarian Neoplasms/drug therapy/*etiology/metabolism

OBJECTIVE: Although radiation therapy (RT) and concurrent chemoradiotherapy (CCRT) are the global standards for adjuvant therapy treatment in cervical cancer, many Japanese institutions choose chemotherapy (CT) because of the low frequency of irreversible adverse events. In this study, we aimed to clarify the trends of adjuvant therapy for intermediate/high-risk cervical cancer after radical surgery in Japan. METHODS: A questionnaire survey was conducted by the Japanese Gynecologic Oncology Group to 186 authorized institutions active in the treatment of gynecologic cancer. RESULTS: Responses were obtained from 129 facilities. Adjuvant RT/CCRT and intensity-modulated RT were performed in 98 (76%) and 23 (18%) institutions, respectively. On the other hand, CT was chosen as an alternative in 93 institutions (72%). The most common regimen of CT, which was used in 66 institutions (51%), was a combination of cisplatin/carboplatin with paclitaxel. CT was considered an appropriate alternative option to RT/CCRT in patients with risk factors such as bulky tumors, lymph node metastasis, lymphovascular invasion, parametrial invasion, and stromal invasion. The risk of severe adverse events was considered to be lower for CT than for RT/CCRT in 109 institutions (84%). CONCLUSION: This survey revealed a variety of policies regarding adjuvant therapy among institutions. A clinical study to assess the efficacy or non-inferiority of adjuvant CT is warranted.
Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Japan/epidemiology ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; *Practice Patterns, Physicians'/statistics & numerical data ; Risk Assessment ; Risk Factors ; Surveys and Questionnaires ; Uterine Cervical Neoplasms/radiotherapy/*therapy

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.
Biomedical Research/*trends ; Breast Neoplasms/therapy ; Combined Modality Therapy ; Dioxoles ; Endometrial Neoplasms/therapy ; Female ; Genital Neoplasms, Female/genetics/*therapy ; Humans ; Immunotherapy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/prevention & control/therapy ; Papillomavirus Vaccines ; Precision Medicine ; Tetrahydroisoquinolines ; Uterine Cervical Neoplasms/prevention & control/therapy/virology ; Uterine Neoplasms/therapy