Combined-modality therapy for gastric cancer

Gastric cancer has a poor prognosis. It is often diagnosed at an advanced stage, and potentially curative treatments often can not be exercised. Even when a curative surgical resection is possible, only a minority of patients survive beyond 5 years, and locoregional failures are frequent among patients undergoing curative resections. Recently, the use of postoperative adjuvant chemoradiotherapy has yielded some notable benefits. Earlier studies have shown survival benefits in patients undergoing chemoradiotherapy for locally advanced unresectable gastric cancer. The recently reported Intergroup 0116 trial compared surgery alone with surgery plus postoperative chemotherapy plus chemoradiotherapy. Superior overall and disease-free survival rates among patients given combined-modality postoperative therapy were observed. These results established a new standard of care for patients following resection of gastric carcinoma. Preoperative combined-modality chemoradiotherapy may improve resectability, and is under investigation at the University of Texas M. D. Anderson Cancer Center. The development of novel radioenhancers and the selection of therapy on the basis of molecular determinants of response may result in much-needed advances in this field.     

Surgical strategies in patients with gallbladder cancer: nihilism to optimism

INTRODUCTION: Gallbladder cancer is an aggressive disease with dismal results of surgical treatment and a poor prognosis. However, over the last few decades selected groups have reported improved results with aggressive surgery for gallbladder cancer. METHODS: Review of recent world literature was done to provide an update on the current concepts of surgical treatment of this disease. RESULTS: Long-term survival is possible in early stage gallbladder carcinoma. Tis and T1a gallbladder carcinoma can be treated with simple cholecystectomy only. However, in T1b and beyond cancers, aggressive surgery (extended cholecystectomy) is important in improving the long-term prognosis. Laparoscopic cholecystectomy should not be performed where there is a high index of suspicion of malignancy due to the frequent association with factors (such as gallbladder perforation and bile spill) which may lead to implantation of cancer cells and dissemination. Surgical resection for advanced carcinoma gallbladder is recommended only if a potentially curative R0 resection is possible. Aggressive surgery with vascular and multivisceral resection has been shown to be feasible albeit with an increase in mortality and morbidity. However, the true benefit of these radical resections is yet to be realized, as the actual number of long-term survivors of advanced gallbladder carcinoma is few. CONCLUSIONS: Surgery for gallbladder carcinoma, like other malignancies, has the potential to be curative only in local or regional disease. Pattern of loco-regional spread of disease dictates the surgical procedure. Radical surgery improves survival in early gallbladder carcinoma. The long-term benefit of aggressive surgery for advanced disease is unclear and may be offset by the high mortality and morbidity.     

Systemic therapy for biliary tract cancers

Biliary tract cancers (BTCs) are invasive carcinomas that arise from the epithelial lining of the gallbladder and bile ducts. These include intrahepatic, perihilar, and distal biliary tree cancers as well as carcinoma arising from the gallbladder. Complete surgical resection offers the only chance for cure; however, only 10% of patients present with early-stage disease and are considered surgical candidates. Among those patients who do undergo "curative" resection, recurrence rates are high; thus, for the majority of BTC patients, systemic chemotherapy is the mainstay of their treatment plan. Patients with unresectable or metastatic BTC have a poor prognosis, with a median overall survival time of <1 year. Despite a paucity of randomized phase III data, a consensus on first-line systemic therapy is emerging. In this review, we discuss the clinical experience with systemic treatment of BTC, focusing on the rationale for a first-line regimen as well as future directions in the field.     

胆道癌围手术期治疗进展北大核心

胆道癌恶性程度高,预后极差,5年生存率不足5%。手术切除是目前胆道系统肿瘤唯一可能治愈的方法,但存在根治性切除率低、术后易复发等难题。围手术期治疗主要针对局部晚期恶性肿瘤,以放化疗为主要手段,能够提高手术切除率,防止疾病复发,最终达到延长生存期的目的。目前已有多项胆道癌围手术期治疗模式的临床研究结果公布,为局部晚期胆道癌的综合治疗带来了新的选择。本文围绕新辅助治疗、辅助治疗和转化治疗三部分就局部晚期胆道癌的围手术期治疗热点及研究现状进行综述。     

Transthoracic En-bloc Esophagectomy

In patients with esophageal carcinoma surgical resection remains the standard of curativetreatment.For locally advanced tumors (pT1sm-pT3) transthoracic esophagectomy with extended lym-phadenectomy is the standard surgical procedure since it offers a complete removal of the primary tumorand possible lymph node metastases.This surgical resection is appropriate for squamous cell but alsoadenocarcinoma of the esophagus because both histological entities demonstrate a lymphatic spread tothe abdominal compartment and the upper mediastinum.In-hospital mortality rates are between 6% and9%;anastomotic leakage and pulmonary complications mainly contribute to postoperative morbidity.Interms of 5-year survival the transthoracic procedure offers a better prognosis compared to the transhiatalresection.     

经胸食管全切除术

In patients with esophageal carcinoma surgical resection remains the standard of curative treatment. For locally advanced tumors (pTlsm-pT3) transthoracic esophagectomy with extended lymphadenectomy is the standard surgical procedure since it offers a complete removal of the primary tumor and possible lymph node metastases. This surgical resection is appropriate for squamous cell but also adenocarcinoma of the esophagus because both histological entities demonstrate a lymphatic spread to the abdominal compartment and the upper mediastinum. In-hospital mortality rates are between 6% and 9%; anastomotic leakage and pulmonary complications mainly contribute to postoperative morbidity. In terms of 5-year survival the transthoracic procedure offers a better prognosis compared to the transhiatal resection.     

Primary cardiac sarcoma in pregnancy: a case report and review of the literature.

Primary cardiac sarcoma (PCS) is a rare disease with a poor prognosis, because of diagnostic delay, therapeutic difficulties, and high metastatic potential. Surgery is the standard treatment. A case of PCS in pregnancy is reported, with a review of published surgical series of PCSs, focusing on the role of surgery and adjuvant therapy. Prompt surgery improved cardiac function and patients' outcome in comparison with untreated cases. The role of adjuvant treatment was analyzed only in a few series, mainly without distinction between postoperative chemotherapy and radiotherapy; adjuvant therapy improved survival in the larger series of resected PCSs. Only three other cases of PCS in pregnancy were reported. In the present case, resection was performed with no major complication for the mother and the infant. Even if the patient's survival was short, cardiac surgery allowed prolonging of pregnancy until an acceptable possibility of fetal survival was reached. Although resection is not curative in most cases, surgery remains the treatment of choice for PCS and has a definite palliative significance. The role of postoperative chemotherapy and radiotherapy is difficult to ascertain; however, adjuvant chemotherapy seems advisable in high-grade tumors.     

胆囊癌外科治疗的争议与思考

胆囊癌恶性程度高,易侵犯邻近脏器和发生淋巴结转移,且对放化疗不敏感,是预后最差的胆道恶性肿瘤.根治性手术切除仍然是目前唯一有可能治愈胆囊癌的手段,但是关于胆囊癌的手术方式、肝脏切除范围、淋巴结清扫范围、意外胆囊癌的处理等方面仍存在诸多争议.此外,当前免疫治疗和靶向治疗在多种实体瘤中取得巨大成功的背景下,未来外科手术在进...     

Radical surgery for gallbladder cancer: a worthwhile operation?

AIMS: Extended operations are the only chance of a cure for patients with advanced gallbladder carcinoma, but there is no consensus about which subset of patients can benefit. The aim of this retrospective study is to evaluate the results of surgical resection with special reference to the prognostic factors and to long-term survival. METHODS: A retrospective review of 70 patients with a diagnosis of gallbladder cancer treated from 1985-1998 was performed: 33 patients had a curative resection and were included in this study. For stage I disease, simple cholecystectomy was considered curative; in most of the other cases, cholecystectomy was associated with lymph node dissection and liver resection. RESULTS: Hospital mortality and morbidity were 6% and 33%, respectively. Curative resection was associated with an actuarial 5-year survival of 27.4%. Survival of pT1-2 patients was significantly better than that of pT3 (P=0.04) or pT4 patients (P=0.002). Patients with lymph node spread had a poorer prognosis (P=0.06) but four were alive and disease-free with a median survival of 22 months. CONCLUSIONS: Depth of the tumour and lymph node metastases are important prognostic factors. Patients with pT3-4 tumours or regional lymph node spread should be considered for curative resection because long-term survival is possible.     

Long-term follow-up of surgically treated gallbladder cancer patients

AIMS: Palliative attempts have traditionally led treatment of gallbladder cancer but resection offers the only chance for long-term survival. This study investigates the impact of surgery with curative intent in gallbladder cancer treatment and evaluates prognostic factors for survival. METHODS: Two hundred and sixty-seven patients were admitted for surgical therapy. Sixty received resection with curative intent and form the basis of this analysis. RESULTS: R0 resection (n=45) was a highly significant independent survival predictor (P<0.001). All 5-year survivors (n=10) had tumour-free resection margins. Early T stage (P=0.017) and highly differentiated cancer (P=0.008) had a significant better outcome. Nodal spreading increased by local tumour extension and lymphatic involvement decreased patient survival (P=0.018). Patients' age (>75 years) was without influence on long-term survival. CONCLUSIONS: Long-term survival is possible both in elderly patients and in advanced cancer.     

Curative surgery for gastric cancer in the elderly: treatment decisions, surgical morbidity, mortality, prognosis and quality of life

AIMS AND BACKGROUND: Surgical risk is deemed to be higher in the aged population because there are often comorbidities that may affect the postoperative result. This consideration is important for the treatment decision-making for gastric cancer in the elderly. The aim of this study was to identify factors influencing mortality, morbidity, survival and quality of life after curative surgery for gastric cancer in patients aged 75 years and older, and to plan their appropriate management. METHODS AND STUDY DESIGN: From January 1993 to December 2004, 135 patients underwent surgery at our department because of gastric cancer. Ninety-four of these patients (69.6%) underwent potentially curative gastrectomy. A cross-sectional study of 23 patients aged 75 years and older and 71 younger patients who underwent curative gastrectomy was carried out: patient characteristics, tumor characteristics, management, morbidity, mortality, survival, and quality of life were evaluated. RESULTS: Elderly patients had significantly more comorbidities and a poorer nutritional status than younger patients. The surgical procedures were similar in both groups and the overall morbidity rate was 27.9% and the overall mortality rate 8.5%. Medical mortality was significantly higher in elderly patients, and the presence of comorbidities was the only independent factor affecting mortality. The 5-year survival rate was 56.2% in the older group versus 62.1% in the younger group and tumor stage was the only prognostic factor influencing survival. Quality of life after surgery was similar in both groups. The significantly better postoperative functional outcome after subtotal gastrectomy suggested a better compliance of elderly patients with subtotal than total gastrectomy. CONCLUSIONS: In the elderly, surgical strategies must be modulated on the basis of comorbidities, tumor stage and future quality of life. Since elderly patients have no worse prognosis than younger patients, age is not a contraindication to curative resection for gastric cancer. Subtotal gastrectomy should be the procedure of choice mainly in elderly patients as it offers better quality of life.     

Postoperative adjuvant therapy for pancreatic cancer

The majority of patients diagnosed with pancreatic cancer present at an advanced stage, and only a small percentage are considered technically resectable at diagnosis. The overall prognosis for the majority is dismal, with a median survival in untreated cases of only 24 weeks. Even in resected patients the overall 5-year survival rate is generally only 5% to 10%; however, some reports indicate higher 5-year survival rates in patients treated with surgery who are pathologically staged with no lymph node involvement. Even when macroscopically complete resection is achieved, local recurrence (LR) rates are unacceptably high (30% to 70%), which is usually attributed to the difficulty of obtaining microscopically free surgical margins. Microscopic clearance is difficult to achieve because these tumors frequently extend into the peripancreatic tissues (e.g., retropancreatic fat), abut or invade the adjacent large vessels (the portal vein and superior mesenteric artery), and have a propensity to invade the lymphovascular and perineural space. Other common sites of failure after attempted curative resection include metastasis to the liver and the peritoneal cavity. Patients who present with pancreatic cancer, and for whom curative surgery is deemed possible, are thus potential candidates for adjuvant therapy because of the high local failure rate following resection alone. The radiotherapy dose that can be achieved in the postoperative setting for pancreatic cancer is limited because of the proximity of critical structures (e.g., the kidney, liver, small intestines, stomach, and spinal cord). Newer techniques such as conformal radiotherapy and intensity-modulated radiotherapy have the advantage of being able (theoretically) to precisely localize the dose to the target volume while reducing the dose to critical structures. These techniques may potentially enable the tumorcidal dose to be increased; however, they are only now becoming widespread. Systemic radiation-sensitizing chemotherapy is also a promising approach to take advantage of additive or synergistic effects with radiation locally, and for the sterilization of systemic disease. This concept of concomitant chemotherapy with radiotherapy, or chemoradiotherapy, has proved effective in a number of sites, including the anal canal, rectum, lung, and pancreas. The recent trials reviewed here varied considerably in terms of the total dose and technique used, and the choice of radiation sensitizing treatment.     

Liver resection for intrahepatic cholangiocarcinoma

AIMS AND BACKGROUND: Intrahepatic cholangiocarcinoma (IHCC) is the second most common primary liver cancer, representing 10% of all primary liver malignancies. Despite the increase in its incidence, this tumor remains extremely rare in Western countries and few reports detailing experience with surgical resection have been published. The aim of this study was to analyze the experience with resection of IHCC in our center. METHODS: From 1987 to 2003 we observed 35 patients with IHCC; 15 of them (42.8%) were submitted to hepatic resection. IHCCs accounted for 13% of all liver resections for primary liver tumors carried out at our center during this period. According to the classification of the Liver Cancer Study Group of Japan, the tumors were classified as "mass-forming" in 14 cases and as "periductal" in one case. Major resections were performed in ten cases and minor resections in five cases. In the patient with a periductal tumor a major resection was performed along with excision of the main biliary confluence. In 14 cases (93.3%) tumor-free resection margins were obtained. RESULTS: The intraoperative mortality was nil and the postoperative mortality 6.6%. The postoperative morbidity rate was 21.4%. The mean overall survival was 38.4 months, with 86% and 49% one- and three-year survival rates, respectively. Patients with mass-forming tumors and curative resections (R0) (mean survival 40.8 months; one- and three-year survival rates 92.3% and 52.7%), and those with TNM stage I-II tumors (mean survival 43.7 months; one- and three-year survival rates 100% and 66.7%) had a longer survival. The patient with the periductal tumor and R1 resection died after seven months. CONCLUSIONS: These results support a surgical approach based on accurate selection of patients with IHCC and aimed at radical resection whenever possible. The good survival rates observed in R0 resections emphasize the role of radical surgery as the only chance of cure for patients with this tumor.     

Multidisciplinary approaches to intrahepatic cholangiocarcinoma

After hepatocellular carcinoma, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. The etiology of ICC in most patients is not known, but its incidence is on the rise worldwide. There are 3 morphologic subtypes of ICC that can be characterized on cross‐sectional imaging, mass forming, periductal infiltrating, and intraductal growth; and the radiographic characteristics of ICC may vary based on the subtype. Complete surgical resection remains the only potentially curative option for patients with ICC. Routine lymphadenectomy at the time of surgical resection should be strongly considered, because lymph node status provides important prognostic information. After surgery, the 5‐year survival rate for ICC remains poor at only 25% to 35% in most series. Although numerous clinical trials have been conducted using a variety of chemotherapy regimens to treat ICC, systemic options for ICC remain limited. Doublet gemcitabine and cisplatin therapy is currently considered the standard‐of‐care first‐line therapy for patients with advanced disease. Because ICC is typically confined to the liver and systemic chemotherapy traditionally has had only limited efficacy, there has been increasing interest in locoregional therapy. Although locoregional therapy may include intra‐arterial therapies, stereotactic radiotherapy, hepatic artery pump therapy, or ablation, most data are limited. The purpose of this article was to provide a multidisciplinary appraisal of the current therapeutic approaches to ICC. Cancer 2013 ;119:3929–3942. © 2013 American Cancer Society.     

Total mesorectal excision for middle and lower rectal cancer: a single institution experience with 337 consecutive patients

BACKGROUND AND OBJECTIVES: There have been reports on improved prognosis after TME for middle and lower rectal cancer. No prospective randomized studies have yet been performed. This is a large single institution series evaluating its own results of TME. METHODS: This retrospective study analyses data of 337 patients with middle and lower rectal cancer, treated with either curative or palliative intention between 1990 and 1998. RESULTS: Of all patients, 212 had lower rectal and 125 middle rectal carcinomas. The rate of rectal resections with TME was 96%. A total of 223 patients were treated by anterior rectal resection; 92 patients had to undergo abdomino-perineal resection. Ten patients were operated by a Hartmann resection. Postoperative morbidity was 35% with a leakage rate of 9%. Postoperative mortality was 4%. The rate of local recurrence was 8.6%. The 5-year survival rate after curative resection was 69.3%. The multivariate analysis outlined the tumor stage as independent prognostic factor. CONCLUSIONS: In our experience, TME is feasible with acceptable postoperative morbidity and low mortality. The local recurrence rate can be decreased to lower than 10%. The almost 70% 5-year survival rate indicates a clear benefit for the patients. These findings recommend TME as standard procedure for middle and lower rectal cancer.     

Current developments,problems and solutions in the non-surgical treatment of pancreatic cancer

Pancreatic cancer is a common malignant neoplasm of the pancreas with an increasing incidence, a low early diagnostic rate and a fairly poor prognosis. To date, the only curative therapy for pancreatic cancer is surgical resection, but only about 20% patients have this option at the time of diagnosis and the mean 5-year survival rate after resection is only 10%-25%. Therefore, developing new treatments to improve the survival rate has practical significance for patients with this disease. This review deals with a current unmet need in medical oncology: the improvement of the treatment outcome of patients with pancreatic cancer. We summarize and discuss the latest systemic chemotherapy treatments (including adjuvant, neoadjuvant and targeted agents), radiotherapy, interventional therapy and immunotherapy. Besides discussing the current developments, we outline some of the main problems, solutions and prospects in this field.     

Liver-Directed Therapies: Does It Make Sense in the Current Therapeutic Strategy for Patients With Confined Liver Colorectal Metastases?

Nearly half of patients with colorectal cancer will have metastases in the course of their disease and the liver appears to be the most common location for metastases. For patients with confined hepatic colorectal metastases, complete surgical resection is the only chance for cure, with a 5-year postoperative survival rate between 35% and 50%. Over the past 5 years, combinations of chemotherapy with targeted therapies have succeeded in inducing tumoral response and have made curative surgery of initially unresectable liver metastases possible. However despite optimal preoperative treatment, disease in the majority of patients remains unresectable. For patients with liver-limited or liver-dominant metastatic colorectal cancer (mCRC), the current challenges are to explore different locoregional treatments to improve local control, overall survival (OS), and curative resection. In this way, liver-directed therapy, which is defined by injection, infusion, or embolization of chemotherapy or loaded radionuclide (with radioactive yttrium-90) microspheres into the arterial liver vasculature, has been an appealing investigational method for patients with liver-confined mCRC, in whom it has yielded reproducibly higher response rates (RRs) than conventional intravenous therapy. In this article, we propose to review, compare, and discuss the clinical benefit, the current indications, and the optimal use of liver-directed therapies for patients with liver-dominant mCRC.     

Management of carcinoma of the gallbladder: a single-institution experience in 16 years

BACKGROUND: Radical surgery is the only curative treatment for carcinoma of gallbladder. This study aimed to evaluate the outcome of patients with carcinoma of gallbladder managed in a single institution over 16 years. METHODS: From April 1988 to November 2003, 86 patients (29 males, 57 females) were diagnosed to have carcinoma of gallbladder. Tumor staging, treatment modalities and clinical outcome of these patients were evaluated. Thirty-two patients (37%) had early stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage (TNM stage III or IV) disease. Curative treatment by surgical resection was performed in 23 patients (27%). RESULTS: Overall survival was significantly better in patients with curative treatment (1-year: 85%; 2-year: 63%; 3-year: 55%) than those with palliative treatment (1-year: 11%; 2-year: 3%; 3-year: 0%; P < 0.01). Using Cox regression model, curative treatment was the only independent prognostic factor affecting overall survival of patients with carcinoma of gallbladder. A significantly better survival was associated with curative treatment compared with palliative treatment in patients with incidental gallbladder cancer. The median survival was 33.9 months for the curative treatment group versus 3 months for the palliative treatment group (P = 0.0001). CONCLUSION: Favorable survival outcome can be achieved in patients with carcinoma of gallbladder after curative resection.     

原发性肝癌临床分期标准的探讨

目的：探讨适合我国原发性肝癌的临床分期标准。方法：回顾性分析复旦大学肝癌研究所收治的427例原发性肝癌病例的临床资料，分析各分期标准所含指标与预后的相关性、各分期标准对根治性切除率及术后预后的反映程度。结果：肿瘤大小、数目、合并癌栓及肝硬化为肝癌患者预后的相关因素，具体分组及肝癌专业委员会制定的标准较一致，在反映根治性切除率及术后预后时，肝癌专业委员会制定的分期标准比较有价值。结论：在几种分期标准中，肝癌专业委员会制定的分期标准最适合我国肝癌患者的临床实际。     

Surgical treatment for metastatic malignancies. Anatomical resection of liver metastasis: indications and outcomes

Hepatectomy may be the only treatment modality for the cure of colorectal liver metastasis. However, whether to perform nonanatomical resection or anatomical resection remains unclear. Original articles in English on liver metastasis, including reports that dealt with case series of more than 50 curative hepatectomies, were reviewed, and the current status of surgical treatment for colorectal liver metastasis was summarized, with a special emphasis on the relevance, indications, and outcomes of anatomical hepatectomy. Anatomical hepatic resection was performed in 63% of the patients. For patients who were treated by curative hepatectomy, including both anatomical and nonanatomical resection, the morbidity rates, mortality rates, 5-year survival rates, and rates of hepatic recurrence were 23%, 3.3%, 34%, and 41.2%, respectively. In 73 articles that each analyzed more than 50 patients treated with potentially curative hepatectomy, the incidence of anatomical resection exceeded 50% in 56 series, while anatomical resection was performed in fewer than 50% of the patients in 17 series. A comparison between these two groups naturally revealed a remarkable difference in the incidence of anatomical resection (72% versus 34%), but no difference in terms of morbidity; mortality; survival rates at 3, 5, and 10 years; or rate of hepatic recurrence. The profile of liver metastasis related to prognosis was generally advantageous to patients treated with nonanatomical resection, and this may have nullified the survival advantage of anatomical hepatectomy over nonanatomical resection. Anatomical resection provides a higher probability of coresecting microscopic invasions that are predictable but undetectable, and can be recommended as a standard procedure for locally advanced metastatic liver cancer.