肝移植治疗肝脏恶性肿瘤的长期疗效及预后危险因素

目的 总结肝移植治疗肝脏恶性肿瘤的长期疗效,筛选影响移植后肿瘤复发的危险因素.方法 对单中心189例肝脏恶性肿瘤患者行肝移植的临床资料进行回顾性分析.根据肿瘤临床病理类型分别计算受者累积存活率,分析肿瘤临床病理类型与肝移植术后肿瘤复发间的关系,筛选影响肿瘤复发的相关危险因素.结果 189例中围手术期死亡19例,170例进入随访期,随访率为98.8 %.其中166例的原发疾病为原发性肝癌,3例为肝门部胆管癌,1例肝转移癌.166例原发性肝癌肝移植者术后1、3、5和10年的总体存活率分别为52 %、38 %、36 %和36 %,其中符合米兰标准者(49例)的存活率分别为96 %、87 %、87 %和87 %,超出米兰标准者(136例)的存活率分别为42 %、26 %、24 %和24 %(P＜0.05).肿瘤复发是造成肝癌肝移植受者随访期死亡的最主要原因(92.5 %).3例肝门部胆管癌和1例肝转移癌肝移植受者均于术后2年内肿瘤复发.符合米兰标准的肝癌肝移植受者术后肿瘤复发率(10.2 %)显著低于超出米兰标准者(68.4 %,P＜0.05).而在超出米兰标准者中,无大血管侵犯者移植后肿瘤复发率(95.3 %)显著低于肿瘤侵犯大血管者(55.9 %,P＜0.05).以他克莫司为主要免疫抑制剂的受者的肿瘤复发率(46.2 %)低于应用环孢素A者(68.3 %,P＜0.05).移植术前肝肿瘤经皮穿刺射频消融(RF)治疗可降低受者术后肿瘤复发风险(P=0.039,OR=0.293),而术前外周血乙型肝炎病毒(HBV)DNA＞104拷贝/L是移植术后肿瘤复发的高危因素(P=0.016,OR=2.294).结论 对于符合米兰标准的肝癌患者而言,肝移植的远期疗效较好;而合并大血管侵犯者肝移植的预后不佳.移植前RF治疗有助于降低术后肿瘤复发风险,移植等待期应高度重视抗HBV治疗.

Abstract：

Objective To investigate the long-term survival of the recipients with liver malignant tumors receiving liver transplantation and determine the risk factors of tumor recurrence after liver transplantation.Methods The follow-up data of the orthotopic liver transplantation for liver malignant tumors during 1999-2010 were retrospectively analyzed.The survival rate of different pathological tumor types was analyzed respectively.The tumor recurrence rate,mortality and morbidity,and the risk factors of the tumor recurrence were also analyzed.Results 170 recipients were followed up.The follow-up duration ranged from 8-132 months.The general 1-,3-,5-,10-year survival rate was 52 %,38 %,36 %,and 36 % respectively.The 1-,3-,5-,10-year survival rate of HCC matching Millan Criteria was 96 %,87 %,87 %,87 %,while that of HCC exceeding Millan Criteria was 42 %,26 %,24 %,24 % respectively(P<0.05).Tumor recurrence was the main course of the death during follow-up period(92.5 %).The recurrence rate of HCC matching and exceeding Millan Criteria was 10.2 %,and 68.4 % respectively(P<0.05).Among the recipients exceeding Millan Criteria,the recurrence rate of HCC with and without blood vessel invasion was 95.3 %,55.9 % respectively(P<0.05).Radiofrequency ablation before transplantation could decrease the risk of tumor recurrence post-transplantation(P=0.039,OR=0.293),while the high HBV-DNA load (>104 copy/L)was the risk factor of tumor recurrence.Conclusion Orthotopic liver transplantation is an effective and safe treatment for hepatocellular carcinoma matching Millan criteria.Blood vessel invasion is regarded as the contraindication of the liver transplantation of HCC.RF is an effective bridging therapy for the HCC patients,and anti-virus therapy is important during transplant waiting period.     

Hepatic cryotherapy for liver tumors

A high-efficiency hepatic cryosurgical unit has been developed and evaluated. It is capable of simultaneously driving three implantable insulated cryoneedle probes. The system has been used to treat 18 patients with secondary and 4 patients with primary liver cancer: open (n=12), total laparoscopic (n=6), laparoscopic assisted (n=4). In three patient laparoscopic cryotherapy was repeated inside 6 months.Intraoperative bleeding was encountered in three patients undergoing high-volume hepatic freezing but the bleeding was easily controlled. A fall in the core body temperature was encountered in 10 out of 22 patients and averaged 0.4°;C. There was one postoperative death from liver failure in an 80-year-old patient in whom a large hepatoma was frozen. The most consistent postoperative biochemical change was hyperbilirubinaemia (n=3). A right-sided pleural effusion developed in two patients after freezing of lesions on the superior surface of the right lobe.A survival benefit was encountered in three patients, one with central cholangiocarcinoma and the other two with large solitary secondary deposits (melanoma, colon cancer). Seven patients with multiple metastases and two patients with large hepatomas developed recurrence at the frozen site or elsewhere in the liver inside 12 months of follow-up and no clinical benefit could be demonstrated by cryotherapy in this group. In nine patients, the follow-up has been too short (<18 months) to permit any conclusion on outcome. The current limitations of hepatic cryotherapy are largely due to incomplete tumor destruction. The use of insulated laparoscopic cryoprobes which can be positioned under visual control through the parietes in the optimal site for maximal tumor ablation should enhance the therapeutic efficiency of cryotherapy for both primary and secondary hepatic tumors.     

Therapeutic modalities and prognostic factors for primary and secondary liver tumors

During the past decade considerable progress has been reported in the treatment of primary and secondary hepatic malignancies. Refined techniques in surgery, transplantation, radiotherapy, and chemotherapy apparently have made the delivery of treatment safer. At the same time improved understanding of tumor biology has been incorporated in treatment strategies. More recently specific and nonspecific, active and passive immunotherapies have excited wide interest, and information from the first randomized studies is now available. We review current treatment options for primary and secondary hepatic malignancies in an attempt to extract plausible treatment guidelines and to identify promising future directions.

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Resumen En el curso del último decenio se ha informado considerable progreso en el tratamiento de los neoplasmas primarios y secundarios del hígado. Neuvas y refinadas técnicas en cirugía, trasplante, radioterapia y quimioterapia han aportado mayor seguridad a las modalidades de tratamiento. Al mismo tiempo, existe una mejor comprensión de la biología tumoral, la cual ha sido debidamente incorporada en las estrategias terapéuticas. Más recientemente, se ha despertado gran interés en cuanto a la immunoterapia específica y no específica, activa y pasiva, y ya se dispone de información sobre los primeros estudios randomizados. En el presente artículo hacemos una revisión de las opciones terapéuticas para los neoplasmas primarios y secundarios del hígado con la intención de definir guías terapéuticas plausibles y de identificar modalidades promisorias para el futuro.

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Résumé Pendant la dernière décennic, d'importants progrès ont été enregistrés dans le traitement des tumeurs malignes primitives et secondaires du foie. Des techniques sophistiquées dans les domaines de la chirurgie, des transplantations, de la radiothérapie et de la chimiothérapie ont toutes contribué à rendre ce traitement plus sûre. De même, une meillcure connaissance de la biologie tumorale s'est intégrée dans la stratègie thérapeutique. Plus récemment, l'immunothérapie spécifique comme non spécifique, active ou passive, s'est ajoutée avec intérêt et à présent, les résultats d'études randomisées sont disponibles. Les options thérapeutiques des tumeurs malignes primitives ou secondaires du foie sont discutées afin d'extraire les grandes lignes thérapeutiques et d'identifier les directions futures.

     

Clinical prognostic factors in malignant parotid gland tumors.

OBJECTIVE: To analyze the factors in parotid malignant epithelial tumors influencing recurrences and disease-specific survival. METHODS: We retrospectively reviewed the files of 150 patients treated at our institution, from 1974 to 1998. Twenty-four patients were not treated by surgery and were excluded from this study. The remaining 126 patients were treated with surgery and 74 patients had postoperative radiotherapy. Thirty-three patients were treated with parotidectomy plus neck dissection. Neck lymph node metastasis was found in 22 patients, 5 patients had occult neck metastasis, and 4 periparotid lymph nodes metastasis. The mean age was 49 years old. According to the UICC/1997 TNM Classification, 49 patients were stage I, 27 stage II, 22 stage III, and 28 stage IV. The influence of selected factors on the 10 year disease-specific survival was analyzed using the Kaplan-Meier actuarial method and the log-rank test. RESULTS: Forty patients had mucoepidermoid carcinoma, 18 patients adenocarcinoma NOS, 18 patients acinic cell carcinoma, 15 patients adenoid cystic carcinoma, 11 patients malignant mixed tumor, 11 patients salivary duct carcinoma, and 13 patients other pathology. Twenty-five patients had recurrences: 17 had local recurrences, 4 patients had neck recurrences, and 4 were loco-regional recurrences. Five factors influenced negatively the prognosis: 1) T stage (p.00001), 2) grade (p.00001), 3) + lymph nodes (p.0007), 4) facial nerve dysfunction (p.0001), and 5) age (p.004). Patients with high-grade tumors and high-stage tumors had the worst prognosis according to the multivariate analysis. The 10-year disease-specific survival was 97% for stage I, 81% for stage II, 56% for stage III, and 20% for stage IV. CONCLUSION: The grade of the tumor and stage were the most important prognostic factor. EBM RATING: C.     

Long-term follow up of clear cornea trabeculectomy

We evaluated the long-term results of Cairns' clear cornea "trabeculectomy" performed on the Glaucoma Service of the Wills Eye Hospital in six patients with serious glaucoma. Although postoperative pressures initially were lower in all six, these lower pressures were not maintained. Pressure in three of the patients finally was controlled only after instituting medical treatment, including carbonic anhydrase inhibitors in two. The operation failed in the other three, two of whom underwent further surgeries. We conclude that Cairns' clear cornea trabeculectomy, in itself, is not adequate to control intraocular pressure in cases of serious glaucoma.     

Clinical and pathological data of 10 malignant pheochromocytomas: Long-term follow up in a single institute

BACKGROUND: Malignant pheochromocytomas are rare. Many controversies still exists in clinical practice. We report the clinical and histological data of long-term follow up in 10 patients with malignant pheochromocytoma. METHODS: The clinical charts of 10 patients with malignant pheochromocytoma from a single institute were reviewed. The diagnosis of pheochromocytoma was confirmed at surgery. All patients had metastases in sites where chromaffin tissue was normally absent. RESULTS: The median follow-up period was 5.5 years (range, 2-20 years). Extra-adrenal tumors occurred in four patients including paraganglioma tumors in three cases and bladder tumor in one case. Regional lymph node metastases were noted in six patients. Distant metastases were located in the lungs of two patients, in the bones of two patients and in the liver of one patient. Histological characteristics were not helpful for diagnosis of malignancy and for prediction of prognosis. Metastases were present in postoperative pathology in seven patients. In another three patients, metastases were discovered 6 months to 10 years after surgery. Three patients received chemotherapy and one patient received combination therapy of high-dose (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy and chemotherapy. All patients achieved long-term survival except for two who died of metastasis 1.5 years and 2 years after diagnosis. CONCLUSIONS: Early complete resection and adjunctive lymphadenectomy can cure malignancy. Close long-term follow up for more than 10 years after surgery is necessary in patients with pheochromocytoma. The possibility of malignancy should be kept in mind even though the initial pathology is benign.     

Analysis of prognostic and immunohistochemical factors in gastrointestinal stromal tumors with malignant potential

The aim of this study was to analyze 37 patients with malignant primary gastrointestinal stromal tumors and to compare the findings and their therapeutic implications with those previously reported. The medical records of 37 patients who were diagnosed and operated on between January 1996 and December 2002 were retrospectively reviewed. The patients’ age, tumor size, type of surgery, histologic type, mitotic counts, presence of necrosis, Ki-67 proliferative index, National Institutes of Health 2001 consensus classification, immunohistochemical staining, and recurrence were examined to analyze factors affecting survival. Overall actuarial survival for all patients was 46%. When analyzed by type of resection, the complete resection group (R0 resection) had a mean overall survival of 48.2 +- 6.18 months compared with the patients with incomplete resection (R1-R2) who survived a mean of 10.8 +- 3.2 months (P = 0.00). Univariate analysis showed development of recurrence (P = 0.00), tumor size of 8 cm or greater (P = 0.05), Ki-67 proliferative index greater than 0.82 (P = 0.0448), desmin staining (P = 0.0076), age younger than 49 years (P = 0.0009), and incomplete resection (P = 0.00) to be significantly correlated with a poor survival. In multivariate analysis, desmin staining (P = 0.031), tumor size (P = 0.033), age (P = 0.01), recurrence (P = 0.038), and R0 resection (P = 0.02) were significant independent prognostic factors. We recommend that more careful preoperative and more frequent postoperative follow-up examinations be performed for patients with large tumors, age of younger than 49 years, and Ki-67 proliferative index greater than 0.82.     

Robotic hepatectomy for benign and malignant liver tumors

Minimally invasive hepatectomy for benign and malignant liver lesions has gained popularity in the past decade due to improved perioperative outcomes when     

Long-term follow up of sphincterotomy in spinal cord injured men

OBJECTIVES: The long-term outcome of transurethral sphincterotomy (sphincterotomy) for the management of male quadriplegic patients with neurogenic bladder was examined. MATERIALS AND METHODS: A total of 39 men with at least 5-years follow-up after sphincterotomy at our institute were included in this retrospective analysis. The mean age was 36.2 years (range 15-61). The mean follow-up period was 13.1 years (range 5-27). RESULTS: Of the 39 patients, 30 patients (77%) were successfully maintained in reflex voiding with a condom catheter and remaining 9 patients (23%) have received another urinary management, including 4 suprapubic cystostomy, 2 clean intermittent catheterization and 2 clean intermittent catheterization by care giver. The main reason that required another urinary management was the augmentation in autonomic hyperreflexia due to poor urinary drainage. Analysis of the urodynamic parameters revealed that the detrusor overactivity is hard to occur with time and this would be one of the reasons for the change of urinary management. In addition, the preoperative maximum bladder pressure in patients who has changed the urinary management due to the augmentation in AH was significantly lower than that in patients that has been successfully followed up in reflex voiding. CONCLUSIONS: The long-term outcome of sphincterotomy was relatively good. However detrusor overactivity is hard to occur with time and this would be one of the important points during the postoperative routine follow up.     

Long-term follow up of experimental microvascular grafts using Doppler ultrasound

Non-directional Doppler ultrasound was used to determine patency in prosthetic microvascular grafts in 30 rats over 24 weeks. Examinations were carried out every two weeks and exploration and arteriography were used at intervals during the study to confirm the Doppler findings. Two rats died and were excluded from the study. Twenty-six grafts were patent at the time of examination and these were correctly assessed by the Doppler technique. However, only one of two occluded grafts was correctly identified. Our results suggest that while this technique is sensitive, its specificity is low, and graft exploration may still be required to confirm patency. Doppler ultrasound may prove a useful non-invasive tool for long-term follow-up of experimental microvascular grafts if the false positive rate can be reduced by improved technique and further experience.     

Negative impact of new-onset diabetes mellitus on patient and graft survival after liver transplantation: Long-term follow up

BACKGROUND: Little is known about the long-term consequences of new-onset diabetes mellitus (NODM) after liver transplantation (LTX). METHODS: In a chart review between 1996 and 2004, we evaluated its incidence and possible effect on patient and graft survival. Inclusion criteria were: adult primary LTX; deceased donor LTX without combined organs; and dual immunosuppression with tacrolimus and corticosteroid. Patients who died within six months after LTX were excluded. For analytical purposes, each patient was classified into one of four groups: 1) preLTX diabetes mellitus (DM): established DM before LTX; 2) sustained NODM: NODM sustained > or =6 months; 3) transitory NODM: NODM temporarily existed > or =1 and <6 months; and 4) normal: no DM either pre- or postLTX. Patients who had NODM <1 month due to high-dose steroid (e.g., either immediate postLTX or rejection treatment) were considered as normal. Patient and graft survival was examined using Kaplan-Meier methodology. RESULTS: In all, 778 patients met the inclusion/exclusion criteria: preLTX DM 159 (20.4%), sustained NODM 284 (36.5%), transitory NODM 108 (13.9%), and normal 227 (29.2%). Median follow-up was 57.2 months. There was a significant difference in patient (P = 0.012) and graft survival (P = 0.004) among the groups, with sustained NODM showing the poorest patient and graft survivals. Sustained NODM patients had a significantly higher rate of death due to infection, as well as graft failure due to chronic rejection and late onset hepatic artery thrombosis. CONCLUSION: NODM is a frequent complication with poor patient and graft survival after LTX.     

Risk factors for loss to follow up of pelvis and acetabular fractures

IntroductionPelvic and acetabular fracture incidence is increasing worldwide for more than four decades. There is currently no evidence examining risk factors for loss to follow up in patients with these injuries.MethodsPatients presenting with pelvic and/or acetabular fractures at our institution between 2015 and 2020 were included. Demographic, injury, treatment, and follow up information was included. Excluded patients were those who sustained a pathologic fracture, has a course of treatment prior to transfer to our centre, or expired prior to discharge.Results446 patients, 263 with a pelvic ring injury, 172 with an acetabular fracture, and 11 with combined injuries were identified. 271 (61%) of patients in our cohort followed up in Orthopaedic clinic (p = 0.016). With an odds ratio of 2.134, gunshot wound mechanism of injury was the largest risk factor for loss to follow up (p = 0.031) followed by male sex (OR= 1.859) and surgery with general trauma surgery (OR=1.841). The most protective risk factors for follow up with Orthopaedic surgery were operatively treated pelvic and acetabular fractures (OR=0.239) and Orthopaedic Surgery as the discharging service (OR=0.372).DiscussionNumerous risk factors exist for loss to follow up including male sex, ballistic mechanism, and discharging service. Investigation into interventions to improve follow up in these patients are warranted.     

Long-term follow up of patients with Zollinger-Ellison syndrome (ZES)

We have followed 14 patients with the Zollinger-Ellison syndrome for a median period of 9 years. All patients have suffered from peptic ulcer disease and six of the 14 have had complications such as bleeding or perforated ulcer. Almost half the patients have had diarrhoea as a dominant symptom and 4 patients suffered from multiple endocrine neoplasia. Before 1978, the year when the H2-receptor antagonists were introduced, the majority of the patients were operated with total gastrectomy. After that year there has been no need for gastrectomies, but all but two patients have undergone an explorative laparotomy. We have been able to localize the gastrinoma in 9 of 12 operated patients; in 7 cases it was localized within the gastrinoma triangle. Three of the patients are considered to have been cured after surgery. Eight patients have needed adjuvant acid-reducing medical therapy. Five of these have been failures to high doses of H2-receptor antagonists and have been successfully treated with omeprazole. Five patients have died during the follow-up period and death in two of these cases was related to tumor progression.     

Long-term prognostic factors after thrombolysis for lower limb ischemia

OBJECTIVE: This study assessed prognostic factors regarding long-term outcome for amputation and death among patients who underwent intra-arterial thrombolysis due to lower limb ischemia. METHODS: Consecutive patients with intra-arterial thrombolysis due to lower limb ischemia treated at the Department of Vascular Diseases, University Hospital of Malm?, between January 1, 2001, and December 31, 2005, were retrospectively reviewed. A multivariate Cox regression analysis was performed to determine independent predictors for amputation and death. RESULTS: A total of 220 intra-arterial thrombolysis procedures were performed in 195 patients (46% women). Median age was 73 years. Complete and partial thrombolysis was obtained in 41% and 38%, respectively. Hemorrhagic complications were documented in 33%, but only 6% (13 of 220) were interrupted. The amputation rate was 26% and mortality was 35% during a median follow-up of 32 months. Degree of lysis (hazard ratio [HR], 4.8; 95% confidence interval [CI], 2.4-9.7; P < .001), motor deficit at admission (HR, 4.0; 95% CI, 1.8-8.7; P = .001), foot ulcers (HR, 7.2; 95% CI, 2.2-23.4; P = .001), and ischemic heart disease (HR, 2.3; 95% CI, 1.1-4.8; P = .024) remained as independent factors associated with amputation. Renal insufficiency (HR, 2.4; 95% CI, 1.4-4.2; P = .003), ischemic heart disease (HR, 2.1; 95% CI, 1.2-3.7; P = .007), cerebrovascular disease (HR, 2.2; 95% CI, 1.2-4.0; P = .009), foot ulcers (HR, 3.2; 95% CI, 1.2-8.6; P = .019), and acute lower limb ischemia (HR, 3.4; 95% CI, 1.1-10.1; P = .028) remained as independent factors associated with mortality. CONCLUSIONS: Thrombolysis is successful, with few major complications in most patients with lower limb ischemia. Patients with ischemic heart disease and foot ulcers are at higher long-term risk for both amputation and death. A lesser degree of lysis and motor deficit were associated with higher amputation rates. The presence of such negative prognostic factors may help clinicians to deny further invasive vascular treatment. Renal insufficiency, cerebrovascular disease, and acute lower limb ischemia were associated with increased mortality.     

Long-term follow up of argon laser trabeculoplasty in pigmentary glaucoma.

Nine eyes in nine patients with pigmentary glaucoma were treated with argon laser trabeculoplasty (ALT). The mean age of the patients at the time of treatment was 35 years (range, 25 to 46 years); the mean follow up after treatment was 5.5 years. The initial pressure-lowering effect of ALT was 53% (15.3 mm Hg), ie, from a preoperative mean of 29.0 mm Hg to a postoperative mean of 13.7 mm Hg the day after ALT. However, the initial response to ALT wore off in 3 months, after which the intraocular pressure settled at a level 14% (4 mm Hg) lower than before treatment. The rate of failure (ie, unstable glaucoma after treatment) was 11%.