Gallbladder Cancer: A Grand Challenge for Every Surgeon Free

To the Editor,

Gallbladder cancer (GBC) is an extremely malignant disease with no specific symptoms. Early clinical diagnosis of GBC is relatively difficult. Radical surgery remains the only curative treatment for GBC, and the optimal extent of surgical resection depends on the tumor staging. Laparoscopic surgery (LRS) is an optional surgery type for GBC. It will not lead to poorer prognosis compared with open surgery and could expedite recovery, thus has become an important treatment for GBC.

We have read with interest the review recently published by Kawahara et al. [1], which summarized the application of LRS in GBC. Although GBC was once regarded as a contraindication for LRS, the authors believed that long-term survival outcome of LRS was comparable to that of open surgery for strictly selected patients with early GBC, and LRS had the advantage of expediting postoperative recovery because of its minimally invasive characteristics [1].

The safety and availability of LS for GBC simple and extended cholecystectomy have been verified in the past decades. A 10-year prospective cohort study proposed that 5-year overall survival (OS) and disease-free survival of LRS is 76.2% and 68.5%, which of open surgery is 74.8% and 66.1% [2]. Retrospective comparative study performed by Delhi University also illustrated that the overall and recurrence-free survival of LRC is oncologically non-inferior to OS for T1b-T2 GBC, with reduced blood loss and complications [3]. All the above-suggested LRSs have not been absolute contraindications. On the contrary, proper and adequate LRS benefits the curation of early GBC.

We agree with the authors’ idea that different surgical methods should be used for different stages of GBC, for instance, simple cholecystectomy and regional lymphadenectomy for Tis and T1a, extended cholecystectomy including surrounding hepatic tissue and radical lymphadenectomy for T1b–T3, hepato-pancreatoduodenectomy for locally advanced GBC [4, 5]. The early development of GBC is usually asymptomatic and GBC has a high propensity to metastasis. Thus, most patients are diagnosed at intermediate to advanced stages [6]. Surgery remains a fundamental part of GBC treatment and is the only potentially curative modality. The goals of resection include cholecystectomy to obtain clear margins and accurate tumor staging [7], for which performing an extrahepatic bile duct resection and hepaticojejunostomy in partial T2–T3 patients or conducting hepato-pancreatoduodenectomy in locally advanced patients is necessary [5]. Considering that GBC is difficult to diagnose early and readily invades the lymphatic system, regional lymphadenectomy involving six or more lymph nodes is recommended for each T stage [4, 5, 7] (see Table 1).

Although surgical resection provides the only probability for cure, the nonsurgical treatment of GBC is still in great need to achieve long-term survival, especially for patients with locally advanced GBC. Nonsurgical multidisciplinary and personalized approach is tailored to specific phases, incorporating chemotherapy, radiotherapy, and palliative care [8]. At the moment, it is recommended to administer capecitabine or gemcitabine/cisplatin for T1b–T2 postoperative patients consist with BILCAP trial [9], PRODIGE-12/SWOG S0809 trial [10], and GECCOR-GB trial [11]. The latter two also proposed that capecitabine concurrent with chemoradiation was an effective, tolerable, and promising adjuvant strategy when it comes to patients with high risks, including R1 margins and positive lymph nodes [9, 10]. As for locally advanced GBC, it is recommended to administer resection and adjuvant therapy as mentioned above in resectable conditions, and neoadjuvant therapy can effectively downstage tumor for follow-up cure in unresectable conditions [11].

Unlike other cancers, there are no tests or procedures that are used routinely for early detection or prevention of GBC. And GBC is usually detected at advanced stages because of lack of symptoms in the early stage [12]. Usually, the symptoms include loss of appetite, chronic abdominal discomfort, weight loss, itching, scleral icterus, and jaundice [13], which are all nonspecific symptoms also commonly seen in various types of digestive diseases. Thus, early differential diagnosis has become particularly important. Our early research found that gallbladder carcinoma is an extremely malignant disease with a 5-year survival rate of less than 5% [13]. And it is often difficult to distinguish between GBC and diseases such as gallstones, gallbladder adenomyosis, and cholecystitis [13]. Ultrasound, enhanced CT, MRI are often used in combination. Compared to multidetector CT, high-resolution ultrasound (HRUS) has higher interobserver agreement between reviewers and is not inferior in the sensitivity, specificity, and accuracy to MRI and invasive MRCP [14]. We believe that the most accurate examination might be high-resolution ultrasound, which can help distinguish early-stage wall-thickening type GBC from other benign diseases [13]. Although techniques of imaging and LRS have been advancing, the diagnosis and curative treatment of GBC are still hardly achievable [15], with median OS ranging from 3 to 22 months [16].

In conclusion, the review of Kawahara et al. [1] well summarized corresponding surgical approach according to the GBC T staging, which provides a good guidance for surgeons on laparoscopic treatment for GBC. However, more multicenter prospective studies are needed to confirm the safety and efficacy of LRC for GBC.