胆囊癌专题系列文章述评

我们会同<中华消化外科杂志>编辑部组织了4位国内著名的肝胆外科专家,撰写了本期"胆囊癌专题"的一系列文章.这些专家从不同的角度,探讨了胆囊癌这一难以治愈性疾病的诊断和治疗方法,期望引起国内同行的关注,积极开展更加深入的研究.     

Gallbladder cancer--a comprehensive review.

AIM: Gallbladder cancer is the fifth most common cancer involving the gastrointestinal tract, but it is the most common malignant tumour of the biliary tract worldwide. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. This tumour is traditionally regarded as a highly lethal disease with an overall 5-year survival of less than 5%. The marked improvement in the outcome of patients with gallbladder cancer in the last decade is because of the aggressive radical surgical approach that has been adopted, and improvements in surgical techniques and peri-operative care. This article aims to review the current approach to the management of gallbladder cancer. METHODS: A Medline, PubMed database search was performed to identify articles published from 1990 to 2007 using the keywords 'carcinoma of gallbladder', 'gallbladder cancer', 'gallbladder neoplasm' and 'cholecystectomy'. RESULTS AND CONCLUSIONS: The overall 5-year survival for patients with gallbladder cancer who underwent Ro curative resection was reported to range from 21% to 69%. Laparoscopic cholecystectomy is absolutely contraindicated when gallbladder cancer is known or suspected pre-operatively. Patients with a pre-operative suspicion of gallbladder cancer should undergo open exploration and cholecystectomy after proper pre-operative assessment. For patients whose cancer is an incidental finding on pathological review, a second radical resection is indicated except for Tis and T1a disease. There is still controversy for the optimal management of T1b disease. Although the role of surgery for advanced disease remains controversial, patients with advanced gallbladder cancer can benefit from radical resection, provided a potentially curative Ro resection is possible. There is still no effective adjuvant therapy for gallbladder cancer.     

腹腔镜胆囊切除术后常规病理检查的必要性探讨

目的:探讨腹腔镜胆囊切除术(LC)后胆囊常规病理检查的必要性。方法:搜集华西医院病理科5年间的全部胆囊病理报告,找出其中LC术后意外胆囊癌患者,并分析其临床资料。结果:LC术后意外胆囊癌的发生率约为0.28%(36/12 969),88.9%(32/36)为腺癌,58.3%(21/36)为原位癌和早期胆囊癌(T1a和T1b)。结合术前影像学检查,术中通过观察及胆囊标本触摸,成功辨认出34例(94.4%)意外胆囊癌患者存在的可疑病变,遗漏1例原位癌和1例T1a期患者。结论:绝大多数意外胆囊癌患者均可在术中发现可疑病变,极少数肿瘤处于极早期无法发现者,单纯的胆囊切除已达有效治疗。因此,LC术后常规的行胆囊病理检查的必要性有待商榷。     

Does “Clinical” R0 Have Validity in the Choice of Simple Cholecystectomy for Gallbladder Carcinoma?

BACKGROUND: This study was designed to evaluate the survival outcomes of patients undergoing simple cholecystectomy and to investigate which patients would benefit from cholecystectomy alone in treating gallbladder carcinoma. METHODS: The available medical records of patients who underwent cholecystectomy alone for gallbladder carcinomas from August 1992 to February 2005 were retrospectively reviewed. Cancer stages were evaluated by clinical meaning based on the AJCC Cancer Staging Manual, 6th edition. "Clinical" R0, defined as gallbladder confined tumor (pT1-3 with negative resection margin) with cN0 and cM0, was tentatively established to evaluate the quality of simple cholecystectomy. RESULTS: Seventy-five patients underwent cholecystectomy alone for gallbladder carcinomas. Twenty-eight patients were male, and forty-seven patients were female, with their mean age 63.5 years (range, 29-80 years). Forty-one patients (54.7%) underwent laparoscopic cholecystectomy, and thirty-four patients (45.3%) underwent open cholecystectomy. T3 lesions were most common (26 patients), followed by T1 (24 patients), T2 (19 patients), and T4 (6 patients). "Clinical R0" could be defined in 48 patients (63%) after simple cholecystectomy. Multivariate analysis showed that incidental gallbladder carcinoma, T stage, and clinical R0 status were independent prognostic factors of long-term survival. When comparing survival outcomes of clinical R0 according to the T stage, no patients with Tis, T1a, and T1b had cancer-related mortality during follow-up. Especially, in patients with T2 gallbladder carcinomas, the mean survival rate was 68.9 months, and the 5-year survival rate was 77.8%. On the contrary, those with T3 lesions had poor prognoses. CONCLUSION: Cholecystectomy alone could be proper management for well-selected patients with gallbladder carcinomas (incidental gallbladder carcinoma, gallbladder confined carcinoma, clinical R0). More experiences and a proper prospective study must be performed to confirm the meaning of clinical R0 in treating gallbladder carcinoma.     

腹腔镜术中意外胆囊癌的诊断与处理策略

意外胆囊癌是指术前诊断为良性病变,但是在胆囊单纯切除术中或术后病理诊断的胆囊癌,在腹腔镜胆囊切除中这种情况时有发生。提高术前影像诊断准确率可以减少意外胆囊癌发生率,准确的术中快速冰冻病理切片检查能够有效避免二次手术。病理诊断T分期为T1a及Tis期的意外胆囊癌患者,单纯胆囊切除术即可达到根治要求,无需二次手术。而T1b及更高T分期的意外胆囊癌患者,需要接受二次手术。二次手术的手术范围参照胆囊根治性切除的要求,也可以根据T分期来决定肝脏的切除范围和淋巴结清扫范围。     

Long-term results after resection for gallbladder cancer. Implications for staging and management.

BACKGROUND: The surgical management of gallbladder cancer is controversial. There is no consensus among surgeons as to the indications for reoperation or radical resection. OBJECTIVE: The purpose of this study was to examine results of reoperation after an incidental finding of gallbladder cancer after cholecystectomy, and results of radical resection in patients with advanced disease. METHODS: A retrospective review of 149 patients with the diagnosis of gallbladder cancer treated from 1985 to 1993 was performed. Fifty-eight patients were explored and 23 underwent resection for cure. Resection included trisegmentectomy in nine patients and bile duct resection in ten patients. Seventeen patients underwent re-exploration after an incidental finding of gallbladder cancer at initial cholecystectomy. RESULTS: Surgical resection is associated with an actuarial 51% 5-year disease-free survival rate, with a median follow-up time of 48 months. Eight patients are alive beyond 50 months. There were no operative deaths; the perioperative morbidity rate was 26%. Nodal status is the most powerful predictor of outcome. Two patients with T4, NO disease are alive without evidence of disease beyond 4 years. Thirteen of the 17 patients (76%) undergoing reoperation after simple cholecystectomy for T2 or T3 tumors had residual disease. CONCLUSIONS: Patients with nodal metastasis beyond the pericholedochal nodes should not be considered for curative resection. Tumors staged T4, NO should be included with stage III disease, and resection should be considered. Re-resection of T2 or T3 tumors after simple cholecystectomy is likely to include residual disease and should thus provide the only chance for long-term survival.     

Spilled gallstones during laparoscopic cholecystectomy

Introduction

Incidental gallbladder cancer is found in 0.6–2.1% of patients undergoing laparoscopic cholecystectomy for symptomatic gallstones. Patients with Tis or T1a tumours generally undergo no further intervention. However, spilled stones during surgery may have catastrophic consequences. We present a case and suggest aggressive management in patients with incidental gallbladder cancer who had spilled gallstones at surgery.

Case History

A 37-year-old woman underwent a laparoscopic cholecystectomy for symptomatic gallstones, during which some stones were spilled into the peritoneal cavity. Subsequent histological examination confirmed incidental pT1a gallbladder cancer. Hepatopancreatobiliary multidisciplinary team discussion agreed on regular six-monthly follow-up. The patient developed recurrent pain two years after surgery. Computed tomography revealed a lesion in segment 6 of the liver. At laparotomy, multiple tumour embedded gallstones were found on the diaphragm. Histological examination showed features (akin to the original pathology) consistent with a metastatic gallbladder tumour.

Conclusions

This case highlights the potential for recurrence of early stage disease resulting from implantation of dysplastic or malignant cells carried through spilled gallstones. It is therefore important to know if stones were spilled during original surgery in patients with incidental gallbladder cancer following a laparoscopic cholecystectomy. Aggressive and early surgical management should be considered for these patients.     

Incidentally Detected Gallbladder Cancer- The Controversies and Algorithmic Approach to Management

Incidentally discovered gallbladder cancer (IGBC) is defined as the gallbladder cancer (GBC) diagnosed during or after the cholecystectomy done for unsuspected benign gallbladder disease. Laparoscopic cholecystectomy (LC) is the most common procedure performed for benign gallbladder disease worldwide. Majority of GBC patients have associated gallstones. With the advent of ultrasonography more patients are being diagnosed with gallstones and are being subjected to cholecytectomy. IGBC is found in 0.2–2.9 % of all cholecytectomies done for gallstone disease. It represents 27–41 % of all GBC. Patients with IGBC having Tis and T1a stage, with negative cystic duct margin can be treated by simple cholecystectomy alone. Patients with stage T1b and beyond should undergo restaging, and should be treated with radical re - resection (R0). Residual disease is found in 40–76 % patients on re-exploration. The survival rates of patients undergoing re resection for IGBC is similar to those undergoing primary radical surgery. LC is contraindicated in patients with GBC. Patients presenting post LC should undergo radical re- resection and additional port site excision, as they have a high incidence of port site metastasis. At cholecystectomy for benign gallbladder disease all gallbladder specimens should be opened before closing abdomen and if available all suspicious specimens should be sent for immediate frozen section. All gallbladder specimens should be subjected to histopathology examination to avoid missing GBC. The surgeon should have a high index of suspicion for GBC if encountering difficult cholecystectomy for a benign disease, and in patients with atypical clinical and ultrasound findings in high incidence areas.     

Implications of the Index Cholecystectomy and Timing of Referral for Radical Resection of Advanced Incidental Gallbladder Cancer

Introduction

Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection.

Methods

The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19–9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed.

Results

Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19–9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging.

Conclusions

In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability.     

Present status of the diagnosis and treatment of gallbladder carcinoma

Because early carcinoma of the gallbladder causes no specific signs or symptoms, most patients with this disease are diagnosed with advanced-stage tumors. High-resolution ultrasonography and a low index of suspicion for polypoid masses or asymmetric gallbladder thickening represent the best method of early detection. Despite regular preoperative gallbladder imaging, many cancers are only detected intraoperatively or incidentally on pathologic examination. All known or suspected gallbladder cancers should be definitively treated with a laparotomy, not laparoscopic surgery. For early gallbladder cancers (Tis and T1 cancers), simple cholecystectomy is adequate therapy. More advanced-stage carcinomas without distant metastases should routinely be managed with a radical cholecystectomy, which includes partial hepatectomy and regional lymphadenectomy. Any adherent organs should be resected en bloc with the cancer. Pancreatoduodenectomy has been performed in several Japanese centers, but is rarely performed in the West for locally advanced gallbladder cancers. Most patients who undergo curative resection will develop recurrent disease, but there is currently no proven effective adjuvant therapy. Received: February 13, 2001 / Accepted: June 18, 2001