Liver-directed therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. This disease can be treated through several surgical and nonsurgical approaches. Although the only curative options for patients with HCC are surgical (resection or transplantation), most patients unfortunately present with advanced neoplastic disease or experience the effects of chronic liver disease, making surgical resection implausible. Several additional options are available for treating this population. Ablative therapies such as percutaneous ethanol injection, cryotherapy, radiofrequency ablation, laser ablation, and microwave hyperthermic ablation can be used with varying degrees of success. Transarterial chemoembolization can be used in patients with advanced disease or advanced chronic liver disease that cannot be treated with resection or ablation. This article explores the various liver-directed therapies, including surgical resection, and defines morbidity, mortality, and survival for each.     

Preoperative imatinib facilitates complete resection of locally advanced primary GIST by a less invasive procedure

Complete resection is the most effective therapy for gastrointestinal stromal tumors (GISTs). Complete resection of locally advanced primary GIST by less invasive procedure is usually difficult at initial diagnosis. Imatinib has been successful in treating locally advanced and metastatic GIST and this report shares the experiences in preoperative use of imatinib for patients with locally advanced primary GISTs. The procedure of treatment and completeness of resection were retrospectively accessed for locally advanced primary GIST. Disease-free survival (DFS) and overall survival (OS) after resection were analyzed. Thirteen patients were treated with imatinib preoperatively. All patients received surgical resection after a median imatinib treatment of 7 months when most tumors shrunk. All patients achieved R0 resection without tumor rupture. Two patients received an en-bloc multivisceral resection for the invasion of surrounding organs and 3 patients underwent Mile’s operation for a low rectal tumor. Eleven patients were disease-free. Median DFS or OS had not been reached, while 1- and 3-year DFS were estimated to be 92.3 and 76.9 %, respectively. 1- and 3-year OS were both estimated to be 100 %. Preoperative use of imatinib is useful in locally advanced primary GIST by downsizing the tumor in most patients and facilitating complete resection through less invasive procedures without tumor rupture.     

Recurrence-associated mortality in patients with differentiated thyroid carcinoma

Differentiated thyroid carcinoma (DTC) is associated with prolonged natural history, and even recurrent tumor is not necessarily followed by increased mortality. Prognostic factors and different treatment strategies, therefore, are difficult to assess. One hundred and fifty-seven patients were followed in our clinic. In an attempt to predict mortality from this tumor, we evaluated the risk factors in 36 patients who presented with recurrent disease. Ten of these patients died. Age above 40 years at initial diagnosis was the predominant risk factor associated with 44% mortality after recurrence. Male sex, lack of radioiodine treatment, and distant site of initial recurrence were all associated with a trend towards increased mortality. Tumor histology and local invasion or extent of initial surgical treatment failed to affect mortality. In conclusion, this approach may be used to identify those patients who will die from their disease, despite currently available treatment. It remains to be seen, however, if new treatment protocols can be developed to improve the prognosis of these patients. © 1993 Wiley-Liss, Inc.     

局部晚期非小细胞肺癌治疗的争议与共识

肺癌是发病率和死亡率增长最快 ,对人类健康和生命威胁最大的恶性肿瘤。完全性切除是目前治疗肺癌的最好方法。但是 ,仅有约 1/3的肺癌适合于外科治疗 ,另 2 /3的肺癌由于伴有远处转移或侵犯邻近器官而被视为不可手术。近年来 ,随着心血管外科理论和技术在肺癌外科中的应用 ,使得肺切除合并受侵的左心房、胸主动脉、上腔静脉和肺动脉的整块切除成为可能。这些过去被视为外科禁忌证和无治愈希望的局部晚期肺癌 ,不但获得肿瘤完全切除、无肿瘤复发转移 ,而且获得长期生存和良好的生活质量。     

Completion thyroidectomy for differentiated thyroid carcinoma

Completion thyroidectomy is defined as the surgical removal of the remnant thyroid tissue following procedures less than total or near-total thyroidectomy. The extent of surgical management for differentiated thyroid carcinoma (DTC) is controversial. Although some authors advocate subtotal thyroidectomy with lower complication rates, total or near-total thyroidectomy and completion thyroidectomy have been defended by others because of the improved survival and lower morbidity that is comparable with subtotal thyroidectomy. In this study, the incidence of residual tumor and surgical complication rates in patients who underwent completion thyroidectomy were investigated. The medical records of 165 patients undergoing completion thyroidectomy for DTC were reviewed. Seventyseven (46.6%) of these patients were found to have residual tumor in the remaining thyroid tissue. Anaplastic transformation developed in two of these patients. Permanent bilateral recurrent laryngeal nerve palsy occurred in three patients, and permanent hypoparathyroidism was seen in one patient. We recommend completion thyroidectomy as an efficient and safe method of surgical treatment with a low complication rate for DTC.     

Noncurative resection for advanced gastric cancer.

Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a "noncurative resection." The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic involvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis (P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is "noncurative." Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended.     

Right hemicolectomy plus pancreaticoduodenectomy vs partial duodenectomy in treatment of locally advanced right colon cancer invading pancreas and/or only duodenum

IntroductionPancreatic or duodenal invasion by locally advanced right colon cancer is an unusual event whose management still represents a surgical challenge. This review aims to compare results of limited vs. extended resection in case of primary right colon cancer invading pancreas and/or duodenum.MethodsA systematic search in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. All trials describing the surgical treatment of right colon cancer invading pancreas and/or duodenum were considered. A data extraction sheet was developed, based on the Cochrane Consumers and Communication Review Group's data extraction template.Results5-years overall survival was 52% after en bloc pancreaticoduodenectomy plus right hemicolectomy vs. 0 and 25% in case of duodenal resection with correction by direct suture or pedicled ileal flap, respectively. 30-day postoperative morbidity rate was slightly higher after en block resections (12.8%) with respect to duodenal local resection and direct suture or pedicled ileal flap repair (0 and 12.2%, respectively). After extended resection the rate of pancreatico-jejunal anastomotic leakage was 7.7%.ConclusionsIn patients with right colon cancer extended to the pancreas and/or duodenum surgical multivisceral resection is suggested when complete tumour removal (R0) is achievable. Even though no significant differences in postoperative morbidity and mortality have been shown, 5 y OS has improved in extended resections as compared to duodenal local resection with defect repair either by direct suture or by a pedicled ileal flap.     

Therapeutic strategies and long-term results in differentiated thyroid cancer

Differentiated thyroid carcinoma (DTC) is usually an indolent tumor associated with a low mortality. However, DTC, particularly papillary thyroid carcinoma, happens to be a multicentric tumor and tends to spread to the regional lymph nodes in the early stage of the disease; some patients with DTC do die from metastatic or recurrent disease. Despite the small number of these patients, therapeutic strategies designed to prevent such outcomes should be pursued. In this review, we attempt to evaluate the impact of different therapeutic strategies on survival and recurrence. Consequently, we conclude that the surgical approach to DIC should be individualized on the basis of the biologic behavior of the tumor, rather than on the extent of cancer involvement in the thyroid and regional lymph nodes. It is mandatory to expand our efforts to identify high-risk patients more accurately, thereby facilitating more rational approaches to treatment.     

Feasibility and Efficacy of External Beam Radiotherapy after Hyperthermic Isolated Limb Perfusion with TNF-α and Melphalan for Limb-saving Treatment in Locally Advanced Extremity Soft-tissue Sarcoma

Purpose: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and melphalan is associated with a dramatic antitumor effect in locally advanced extremity soft-tissue sarcomas (STS). The aim of this study was to demonstrate the feasibility and efficacy of adjuvant radiotherapy after HILP with TNF-α, IFN-γ, and melphalan and delayed surgical resection.Methods and Materials: Between 1991 and 1995, 34 patients—16 males and 18 females, median age 50 (range 18–80) years—underwent HILP for locally advanced extremity STS. Resection of the residual tumor mass was performed in most patients after 6–8 weeks. Fifteen patients with histopathological viable tumor after resection received adjuvent 60–70 Gy external beam radiotherapy (EBRT) (44%, HILP + EBRT group). Nineteen patients received HILP without adjuvent EBRT (56%, HILP-only group). Five patients in the HILP-only group had also distant metastases (15%) and received HILP as a palliative treatment. Treatment morbidity, local recurrences, and regional and distant metastases were scored.Results: During a median follow-up of 34 months (range 8–54), limb salvage was achieved in 29 patients (85%): 14 patients after HILP + EBRT and 15 patients after HILP only. None of the patients from the HILP + EBRT group developed local recurrences; however, five patients from the HILP-only did (26%) (p < 0.05). Regional metastases were observed in one patient from the HILP + EBRT group (7%) and in two patients from the HILP-only group who were treated with curative intent (14%). Distant metastases occurred in four patients after HILP + EBRT (27%) and in four patients after HILP only with curative intent (29%). The mean morbidity (subjective, objective, medical management, and analytical evaluation) score in both groups was, respectively, 0.33 for skin and subcutaneous tissue and for muscle and soft tissue, 0.34 (HILP + EBRT group) and 0.33 (HILP-only group).Conclusion: Adjuvent EBRT after HILP with TNF-α, IFN-γ, and melphalan and delayed tumor resection of locally advanced extremity STS is feasible and may increase local tumor control without increasing treatment morbidity.     

Surgical management of advanced and recurrent cervical cancer

Since the early 1940s, the incidence of cervical cancer has dramatically decreased due in large part to the work of Papanicolaou and Traut. Successful treatment can now be done using simple or radical surgical intervention for early invasive lesions and radiation therapy for more advanced lesions. However, despite current advances in screening and early treatment, local recurrences still happen and are difficult to treat. The natural history of cervical cancers is that of a slowly growing, locally invasive tumor. As such, it lends itself to radical surgical resection in selected patients prior to distant metastasis. Current advances in intraoperative and postoperative monitoring, as well as improved surgical techniques and devices, have decreased the morbidity and mortality of radical surgical procedures to acceptable levels. Current data associated with these procedures for advanced or recurrent cervical cancer are described.     

Endoscopic assessment and management of early esophageal adenocarcinoma

Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion.     

Surgically proven complete response of stage III non-small cell lung cancer after cisplatin-enhanced radiotherapy. Clinical implications and long-term results

AIMS AND BACKGROUND: Pathologic complete response in locally advanced non-small cell lung cancer is the main end point of combined therapies (chemotherapy and/or radiotherapy). Surgery after an induction treatment can improve local control, allowing the histologic assessment of treatment activity by means of resection or extensive biopsies. METHODS: Thirty patients surgically assessed without viable tumor after concurrent radiotherapy and continuous infusion of low-dose cisplatin, owing to an initially unresectable stage III non-small-cell lung cancer, were the object of evaluation to assess clinical implications, short- and long-term surgical results. RESULTS: The specificity rate of the preoperative restaging was 36.6%. The surgical procedures consisted of 22 resections and of extensive biopsies in 8 cases. The operative mortality was 4% (1/25) for procedures other than right pneumonectomy (3/5). No patient received postoperative chemotherapy. Eleven distant progressions, 4 local recurrences, and 4 new primary tumors were assessed as initial failures. The 8-year overall survival was 36%. CONCLUSIONS: Pathologic complete response after cisplatin-enhanced radiotherapy cannot be satisfactorily assessed by clinical means. Surgery is required to obtain a reliable evaluation; however, right pneumonectomy should be contraindicated because of prohibitive risk. Although an effective local treatment can cure patients with advanced stage III disease, the addition of chemotherapy seems advisable to improve tumor relapse control.     

Postoperative adjuvante Strahlentherapie der Vulva und Vagina

It is widely accepted that adjuvant local radiotherapy of the vulva is indicated for limited resection, deep invasion (>5 mm) and close (<1 cm) or positive surgical margins. Other factors in favour of postoperative radiation therapy are lymph vessel invasion and large tumour size. Adjuvant irradiation of the groins is indicated in patients with positive lymph nodes, in particular in high risk patients (≥2 positive nodes and clinically suspect or fixed ulcerated groin nodes), for whom pelvic radiotherapy should be added to inguinal radiotherapy. In patients with clinically negative nodes, the invasion depth is the most important factor to be taken into account to decide whether adjuvant radiation therapy of the groin is required. The importance of surgical treatment for patients with vaginal cancer, in particular for locally advanced disease, is limited. Adjuvant radiation therapy is therefore rarely performed in these patients and little clinical evidence is available. Adjuvant radiotherapy may therefore be applied, analogue to vulvar cancer, in the few surgical patients with close or positive resection margins and in those patients with positive lymph nodes.     

Initial management and follow-up of differentiated thyroid cancer in children

Children with differentiated thyroid cancer (DTC) often present with metastatic disease and have a high risk for recurrence, but rarely die of the disease. This article reviews DTC in children and discusses current approaches to their initial care and follow-up. These recommendations take into account the greater risk for recurrence and lower disease-specific mortality in these patients. Total thyroidectomy and central compartment lymph node dissection are appropriate for most children, but should be performed by a high-volume thyroid surgeon. Radioactive iodine (RAI) should generally be prescribed for those at very high risk for recurrence or known to have microscopic residual disease, and those with iodine-avid distant metastases. RAI should be considered in other patients only after carefully weighing the relative risks and benefits and the aggressiveness of the clinical presentation, because RAI may be associated with an increased risk for second malignancies and an increase in overall morbidity and mortality. All patients should be treated with thyroid hormone suppression, and follow-up should be lifelong. However, the degree of thyroid hormone suppression and frequency of disease surveillance usually decrease over time as patients are determined to be disease-free.     

Extended multiorgan resection for T4 gastric carcinoma: 25-year experience

BACKGROUND AND OBJECTIVES: In locally advanced gastric carcinoma infiltrating adjacent organs, an extended resection including invaded organs is required to improve the prognosis. We retrospectively analyzed our experience with extended multiorgan resection (EMR) in patients with advanced gastric cancer. METHODS: Between December 1979 and April 2004, 65 patients were resected for extended gastric carcinoma macroscopically invading other organs. Various clinicopathologic factors influencing early and late results were evaluated. Survival rates were calculated according to the Kaplan-Meier method. Prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: The majority of patients (61.5%) did receive a R0 curative resection. In 52 (80%) of the 65 presumed T4 cancers, histologic final analysis confirmed invasion. Postoperative morbidity and mortality was 27.7% and 12.3%, respectively. Actuarial 5-year overall survival (OS) rate was 21.8%. It was significantly better in R0 versus R+ (30.6% vs. 0%, P = 0.001). Multivariate analysis identified curative resection as the strongest predictor of survival (P = 0.002). CONCLUSIONS: Patients with locally advanced gastric carcinoma invading adjacent organs can benefit from aggressive surgical treatment with acceptable morbidity and mortality. However, curative resection is mandatory to improve prognosis.     

儿童晚期肾母细胞瘤的术前化疗分析

目的探讨术前化疗对肿瘤较大或有远处转移的肾母细胞瘤的手术帮助和手术时机的选择。方法回顾性分析16例肾母细胞瘤的诊治过程。Ⅱ期10例,Ⅲ期5例,Ⅳ期1例。16例患儿术前均经影像学检查及穿刺活栓明确诊断。所有病例均予术前化疗后行手术治疗。结果5例瘤肾根治性切除,1例手术过程中发生肿瘤破裂,术后病理检查有镜下残留。在术前化疗后2～3周手术13例,2例因术前化疗后肿瘤坏死彻底未获得术后病理分型,术后化疗方案制定依据术前细针穿刺结果。结论术前化疗可以使肿瘤体积变小,减少肿瘤破溃,改善瘤体对毗邻器官浸润程度,使外科手术变得容易。     

Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment outcomes in patients with ATC reported in the National Cancer Institute's Surveillance, Epidemiology, and End Results data base. METHODS: The cohort consisted of 516 patients with ATC reported to 12 population-based cancer registries between 1973 and 2000. Demographic, pathologic, and treatment data were used for univariate and multivariate survival analyses. RESULTS: The mean patient age at diagnosis was 71.3 years, and there were 171 men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node invasion, and 43% of patients had distant metastasis. The average tumor size was 6.4 cm (range, 1-15 cm). Sixty-four percent of patients underwent surgical resection of their primary tumor, and 63% received external beam radiotherapy. The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age < 60 years, female gender, intrathyroidal tumor, external beam radiotherapy, surgical resection, and combined surgical resection of tumor and radiotherapy were associated with a lower cause-specific mortality. On multivariate analysis, only age < 60 years, an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. CONCLUSIONS: Although most patients with ATC had an extremely poor prognosis, patients < 60 years old with intrathyroidal tumors survived longer. Surgical resection with external beam radiotherapy for ATC was associated with lower cause-specific mortality.     

Treatment of locally advanced rectal cancer with external beam radiation, surgical resection, and intraoperative radiation therapy

To try to improve the local control and survival of patients with locally advanced rectal cancer we have used a combination of high-dose pre-operative radiation therapy to 5,040 cGy followed by surgical resection and intraoperative electron beam radiation therapy (IORT) when there was visible or palpable residual disease, microscopically positive surgical margins, or persisting tumor adherence. A total of 75 patients were taken to surgery for resection +/- IORT who did not have distant metastases. Of the 49 patients with primary tumors, 11 did not have IORT as the tumor was thought to be completely resected. Of these 11, there were two local recurrences and a 3-year survival of 71%. Thirty-six patients with primary tumors had resection (20 complete, 16 partial) plus IORT, with a 3-year survival of 58% and three local failures. Twenty-six additional patients were treated for locally advanced recurrence of whom four could not receive IORT because of pelvic size or the extent of tumor. Of the 22 who received IORT, 7/9 with complete resection, 2/8 with partial resection, and 1/5 with no resection had local control with an overall 3-year actuarial survival of 32%. The local control and survival results in the primary tumors appear favorable compared to other series in the literature and suggest benefit to the use of IORT. For patients treated for local recurrence, local control and long-term survival can be obtained, but the results are not as encouraging as for the primary tumors.     

高分化甲状腺癌侵犯上呼吸消化道的治疗

高分化甲状腺癌侵犯上呼吸消化道的治疗对外科医师很具挑战性,在手术切除全部肿瘤同时,应注意保留重要上呼吸消化道结构功能如吞咽呼吸和发声功能,对部分患者可结合^131I和外放射治疗等辅助性治疗,在保证患者的长期生存率的基础上提高生存质量。本文就其生物学特性、诊断、治疗和预后情况作简要综述。     

局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及131I疗效的关系

背景与目的： 儿童及青少年分化型甲状腺癌（differentiated thyroid cancer,DTC）的分子生物学特征及其临床指导意义尚不明确。本研究拟初步探讨局部晚期或转移性DTC患儿的基因特征分布及其与临床特征及¹³¹I疗效的关系。方法： 采用甲状腺癌相关基因panel（ThyroLead^®）对2020年12月—2021年7月就诊于中国医学科学院北京协和医学院北京协和医院的儿童及青少年侵袭性DTC的原发灶进行测序,并回顾性收集患儿的临床病理学特征及¹³¹I治疗相关资料,分析其基因特征与其临床病理学特征及¹³¹I疗效的关系。结果： 本队列纳入39例局部晚期或转移性患儿,可及数据中所有患儿均存在淋巴结转移,侧方区受累率达91.4%（32/35）,远处转移率达61.5%（24/39）。61.5%（24/39）的患儿检出甲状腺癌相关基因变异,其中以RET融合（38.5%,15/39）和BRAF V600E点突变（12.8%,5/39）最为常见。突变组与非突变组的临床特征差异无统计学意义（P>0.05）。远处转移中,91.7%（22/24）的患儿在¹³¹I治疗后仍呈结构性疗效不佳（structural incomplete response,SIR）状态,其中9例患儿呈放射性碘难治（radioactive iodine-refractory,RAIR）状态。RAIR状态患儿中88.9%（8/9）检出相关基因变异,其中NCOA4/RET融合占62.5%（5/8）。进一步将RET变异组患儿细化分组显示,与其他形式的RET融合相比,NCOA4/RET融合阳性者远处转移率更高（33.3% vs 88.9%,P=0.089）,提示其具有更高的远处侵犯倾向。结论： 局部晚期或转移性DTC患儿的基因突变以融合突变尤其是RET融合为主,其中NCOA4/RET融合阳性者似乎显示出更强的侵袭性,更易呈RAIR状态。