Is cholecystectomy a reasonable treatment option for simple gallbladder polyps larger than 10 mm?

AIM: To determine the relevance of the 10-mm size criterion of the generally accepted surgical indication for gallbladder polyps(GBPs). METHODS: We collected data of patients who were confirmed to have GBPs through cholecystectomy at Samsung Medical Center between January 1997 andDecember 2012. Among the patients who underwent cholecystectomy for GBP, those with a definite evidence for malignancy such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp larger than 20 mm, absence of preoperative imaging study results, and patients having gallstones were excluded. We retrospectively collected and analyzed information on patient’s clinical characteristics, symptoms, ultrasonographic findings, and blood laboratory tests.RESULTS: A total of 836 patients who had undergone cholecystectomy were retrospectively analyzed. Seven hundred eighty patients(93%) had benign polyps, whereas 56 patients(7%) had malignant polyps. Of the 56 patients with malignancy, 4 patients(7%) had borderline GBP(10-12 mm) and a patient had small GBP(< 10 mm) with T2 stage. We conducted an ROC curve analysis to verify the 10-mm size criteria(AUC = 0.887, SD = 0.21, P < 0.001). In the ROC curve for polyp size and malignancy, sensitivity and specificity of the 10-mm size criterion was 98.2% and 19.6%, respectively. The specificity of the 11-mm and 12-mm size criteria was 44.6% and 56%, respectively, whereas the sensitivity of these two size criteria was similar. We defined the GBPs of 10 to 12 mm as a borderline-sized GBP, which were found in 411 patients(49%). In this group, there was a significant difference in age between patients with benign and malignant GBPs(47 years vs 60 years, P < 0.05). CONCLUSION: GBPs larger than 13 mm need immediate excision whereas for borderline-sized GBPs detected in young patients, careful medical observation can be a rational decision.     

症状性胆囊结石胆囊收缩功能测定的临床意义

目的:探讨Ｂ超检查下测定胆囊收缩功能的临床意义和其影响因素。方法:５８例症状性胆囊结石患者Ｂ超检查下测定空腹、脂餐后１小时和脂餐后１．５小时胆囊容积并计算脂餐后胆囊排空率(ＰＧＥＲ),分析胆囊结石的大小、个数及病史与胆囊收缩功能的关系。结果:脂餐后１小时ＰＧＥＲ ４１．８６±２７．９９%(０~８７%),脂餐后１．５小时ＰＧＥＲ４８．８２±２８．８６%(０~８７%),两者间比较无明显差异(ｔ＝１．１８,Ｐ＞０．０５)。研究表明胆囊收缩功能的好差与胆囊结石的个数密切相关(ｘ２＝５．５３,ｐ＜０．０５)。结论:胆囊收缩功能的测定在选择慢性胆囊炎、胆囊结石的治疗方案时是必要的。胆囊收缩功能测定采用脂餐后１小时即可。结石过多或较大及长期的慢性胆囊炎均影响胆囊收缩功能。     

Do the progesterone receptors have a role to play in gallbladder cancer?

Background: Gallstone disease as well as gallbladder cancer are more common in women and female sex hormones may be involved in their etiology. Aim and Methods: To determine whether female sex hormones have a role in the pathogenesis, of gallbladder carcinoma and in its prognosis, we estimated, by enzyme immunoassay, the estrogen and progesterone receptors (ER and PgR) in the gallbladders of 21 patients with gallbladder cancer, 19 patients with cholelithiasis, and 6 patients who underwent incidental removal of essentially normal gallbladder as a component of wider resection. Results: ER were present in the gallbladder mucosa in all the three groups in proportions which were not significantly different (9/21 in carcinoma, 4/19 in gallstones, and 1/6 normal), whereas the expression of PgR was greater in carcinomas (13/18), less in cholelithiasis (4/12), and absent in normal gallbladders. PgR expression was higher in tumors of lower stage (7/7) and lower in advanced disease stage IV tumors (6/11). PgR expression was associated with better disease stage (p=0.05) and significantly longer overall survival (median survival of 301 d vs 54 d) as well as better survival within the same stage (269 d vs 54 d for stage IV disease, p=0.011). Cox’s regression analysis showed that PgR was an independent risk factor (R=0.2283, p=0.0035). Conclusions: Our findings suggest that the female sex hormones may have a role in the pathogenesis of gallbladder cancer and that PgR expression has a prognostic significance. We believe that when this relationship is reaffirmed by larger studies, gallbladder cancer may be treated with appropriate sex hormonal manipulation.     

胆囊息肉样病变203例临床分析

目的　探讨胆囊息肉样病变 (PLG )的临床若干问题 ,提高其诊疗水平。方法　腹部B超检出胆囊息肉样病变患者 2 0 3例 ,其中 3 0例经腹腔镜或剖腹胆囊摘除术 ,对其临床表现与病理特点进行比较。结果　 3 0例患者中男性 12例 ,女性 18例 ,年龄 2 8～ 62岁 ,平均年龄 3 8岁。有症状者 16例 ,占 5 3 .3 3 %。真性肿瘤 5例 ( 16.66% ) ,息肉样病变 2 5例 ( 83 .3 3 % ) ,胆囊增厚 18例( 60 .0 % ) ,合并结石者 4例 ( 13 .3 % )。结论　胆囊息肉样病变属胆囊良性肿瘤 ,但少数有恶变危险 ,建议对单发性胆囊息肉样病变直径≥ 10mm或多发性的直径≥ 12mm、直径 <10mm ,但胆囊壁显著增厚 ( >4mm)及 (或 )伴有结石、有较明显的临床症状和B超动态检查息肉短期增大者应手术治疗。     

Do we need histology for a normal-looking gallbladder?

Background/Purpose

Gallbladder cancer (GBC) is a rare malignancy with poor overall prognosis. Simple cholecystectomy is curative if the cancer is limited to mucosa. We aimed here to investigate the need for routine histological examination of gallbladder.

Methods

We carried out a retrospective review of 2890 final pathology reports of processed gallbladder specimens following cholecystectomy due to gallstones disease. The review covered the 10-year period from 1994 to 2004. The notes of all cases of gallbladder cancer were scrutinized, with particular emphasis on presentation, preoperative diagnostic tools using abdominal ultrasound and computed tomography scan, operative findings, and the histology results.

Results

Gallbladder cancer (GBC) was detected in five specimens (0.17%), dysplasia in six (0.2%), and secondaries to gallbladder in three (0.1%). Histological findings confirmed gallstone disease in 97% and rare benign pathology in 3%. The median age of patients with GBC was 61 years (range, 59–84 years). In all five patients, cancer was isolated from thickened fibrotic wall on macroscopic appearance and spread through all layers of the gallbladder wall. The percentage of thickened-wall gallbladder in this study was 38.02% and the cancer incidence in the thickened wall was 0.45%.

Conclusions

A selective policy rather than routine histological examination of nonfibrotic or thickened-wall gallbladder has to be considered. This will reduce the burden on pathology departments, with significant cost savings.

     

Primary melanoma of the gallbladder： Does it exist？ Report of a case and review of the literature

With the occasion of a case of malignant melanoma of the gallbladder, which appeared to be primary, we have reviewed the literature and the result of this research was that primary melanoma of the gallbladder remains a questionable medical entity. Only few cases of both primary and metastatic gallbladder melanoma have been reported so far, and the only agreement is that surgery is the mainstay treatment. The role of adjuvant chemotherapy, hormonotherapy or immunotherapy for both primary and metastatic disease remains undefined.     

Current status and progress in laparoscopic surgery for gallbladder carcinoma

Gallbladder carcinoma (GBC) is the most common biliary tract malignancy associated with a concealed onset, high invasiveness and poor prognosis. Radical surgery remains the only curative treatment for GBC, and the optimal extent of surgery depends on the tumor stage. Radical resection can be achieved by simple cholecystectomy for Tis and T1a GBC. However, whether simple cholecystectomy or extended cholecystectomy, including regional lymph node dissection and hepatectomy, is the standard surgical extent for T1b GBC remains controversial. Extended cholecystectomy should be performed for T2 and some T3 GBC without distant metastasis. Secondary radical surgery is essential for incidental gall-bladder cancer diagnosed after cholecystectomy. For locally advanced GBC, hepatopancreatoduodenectomy may achieve R0 resection and improve long-term survival outcomes, but the extremely high risk of the surgery limits its implementation. Laparoscopic surgery has been widely used in the treatment of gastrointestinal malignancies. GBC was once regarded as a contraindication of laparoscopic surgery. However, with improvements in surgical instruments and skills, studies have shown that laparoscopic surgery will not result in a poorer prognosis for selected patients with GBC compared with open surgery. Moreover, laparoscopic surgery is associated with enhanced recovery after surgery since it is minimally invasive.     

Long-term follow up of gallbladder polyps

Background and Aim:  The management of gallbladder polyps (GBP) is directly linked to the early diagnosis of gallbladder cancer (GBC). This study aimed to evaluate the malignant risk of GBP.
Methods:  In total, 1558 patients diagnosed with GBP were followed. Neoplastic polyps were defined as GBC and its premalignant lesions. The risk for malignancy was estimated with the cumulative detection rate of neoplastic polyps.
Results:  Thirty-three cases (2.1%) were diagnosed with neoplastic polyps. The cumulative detection rates of neoplastic polyps were 1.7% at 1 year, 2.8% at 5 years, and 4% at 8 years after diagnosis. The size of GBP and the presence of gallstones were risk factors for neoplastic polyps. Polyps ≥ 10 mm had a 24.2 times greater risk of malignancy than polyps < 10 mm. However, 15 of 33 neoplastic polyps (45.5%) were < 10 mm at the time of diagnosis of GBP. During follow up in 36 (3.5%) of 1027 cases, an increase in size was detected; of these, nine (25%) had neoplastic polyps.
Conclusion:  Even small polyps have a risk of malignancy, and careful long-term follow up of GBP will help detect and treat early GBC.     

Extended surgical resection for xanthogranulomatous cholecystitis mimicking advanced gallbladder carcinoma： A case report and review of literature

Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography (ERC) showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right lobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.     

进展期胆囊癌的超声诊断及临床价值探讨

目的探讨进展期胆囊癌的超声特征及临床应用价值。方法回顾性分析了43例经手术和病理证实的进展期胆囊癌的超声特征，并对漏误诊病例进行分析。结果胆囊癌的超声图像分为四型：壁增厚型、蕈伞型、混合型、实块型，同时可观察肝转移、肝浸润、区域淋巴结肿大、胆结石、胆管扩张等征象。结论超声诊断胆囊癌及判断其转移情况符合率高，对临床外科提供了有益的帮助。     

A CASE OF PEDUNCULATED POLYPOID CANCER ASSOCIATED WITH FLAT‐TYPE CANCER OF THE GALLBLADDER

Pedunculated polypoid cancer of the gallbladder ordinarily shows cancer spread within the polyp consisting mainly of adenoma. We experienced a case of pedunculated mucosal cancer associated with flat‐type cancer of the gallbladder without an adenomatous component, the details of which are reported herein. The lesion was first detected by transabdominal ultrasonography (US) as a polypoid lesion of the gallbladder, 5 mm in size. Distinct growth of the lesion was revealed at follow‐up US after a year. Endoscopic ultrasonography showed not only a pedunculated polypoid lesion, 9 mm in size, with a solid internal echo pattern and a nodular surface, but also slight thickening of the surrounding gallbladder wall. Cholecystectomy was performed with a preoperative diagnosis of early gallbladder cancer, and a pedunculated polypoid lesion, 8 × 8 × 3 mm in size with a thin stalk and a nodular contour, surrounded by a widely spreading flat lesion with a coarse‐granular surface, was confirmed. Microscopically, the stalk was 700 µm in size, and both the pedunculated polypoid lesion and flat lesion consisted of well‐differentiated tubular adenocarcinoma limited to the mucosa, without an adenomatous component.     

Epidemiology of gallbladder disease: cholelithiasis and cancer

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps.     

不同手术入路腹腔镜胆囊切除术临床疗效及安全性研究*

目的 观察不同手术入路对腹腔镜胆囊切除术(LC)临床疗效及安全性的影响。方法 2016年1月～2018年1月在我院行LC治疗的136例胆囊良性疾病患者,采用随机数字表法分为A组68例和B组68例。在A组,采用侧方入路剥离胆囊,在B组采用顺行或逆行剥离胆囊。随访3个月。采用视觉模拟量表(VAS)进行疼痛程度评分,采用酶联免疫吸附法检测血清C反应蛋白(CRP)、白介素-6(IL-6)、中性粒细胞弹性蛋白酶(NE)和肿瘤坏死因子-α(TNF-α)。结果 A组和B组手术成功率分别为97.1%和95.6%,分别有2例和3例中转开腹,差异无统计学意义(P>0.05);在术后6 h,A组VAS评分为(3.1±0.6)分,显著低于B组【(4.1±1.0)分,P＜0.05】,在术后12 h,A组VAS评分为(1.5±0.5)分,显著低于B组【(3.1±0.7)分,P＜0.05】;术后,A组血清CRP、IL-6、NE和TNF-α水平分别为(2.9±1.3)mg/L、(3.3±0.7)ng/L、(1.2±0.5)μg/L和(0.9±0.7)ng/L,均显著低于B组【分别为(4.2±1.6)mg/L、(4.8±1.5)ng/L、(2.6±0.9)μg/L和(1.9±0.8)ng/L,P<0.05】;在随访3个月时,A组胆囊破裂、胆囊床渗出等并发症发生率为7.4%,显著低于B组的23.5%(P<0.05)。结论 在腹腔镜胆囊切除术中经侧方入路与顺行或逆行剥离胆囊均能获得满意的临床治疗疗效,但前者在减小创伤和并发症发生方面具有优势,值得临床应用。     

Benign gallbladder lesions mimicking cancer infiltrating the liver

Considering the current improved resectability of advanced gallbladder cancers, differentiation from benign gallbladder lesions mimicking advanced cancer is now a significant problem to be overcome so that unnecessary extended operations can be avoided. During the 4 years from January 1989 to December 1992, we experienced 63 patients with elevated lesions of the gallbladder, including cancer. Among the 59 patients who underwent resection, preoperative imaging diagnostic procedures were suggestive of cancer in 27. In particular, the lesions of 14 patients appeared to be cancerous with hepatic infiltration. Frozen section histological examinations were performed on the specimens of 4 of these patients in whom the findings were inconsistent; all of them were shown non-cancerous. The final diagnoses in these 4 patients were: hyperplastic polyp with foreign body granuloma, xanthofibromatous granulation, localized type adenomyomatosis, and chronic cholecystitis. Resections were performed on the remaining 10 patients who had lesions suspected to be cancerous with infiltration to the liver. Nine lesions were confirmed as cancer by histological examination of the resected specimen. However, the lesion of the remaining patient, who underwent hepatopancreatoduodenectomy, proved after operation, to be a hamartoma with foreign body granuloma. Of the imaging diagnostic procedures, a combination of endoscopic or intraoperative ultrasonography and computerized tomography was most valuable for making the differential diagnosis between gallbladder cancer and benign gallbladder lesions mimicking cancer infiltrating the liver. However, frozen section histological examination should not be omitted before the extended operations are performed, even though en bloc resection is preferable because the procedures used to obtain the specimens have the potential to disseminate viable cancer cells.     

Elevated CA 19-9 portends poor prognosis in patients undergoing resection of biliary malignancies

Background:

Biliary tree malignancies including cholangiocarcinoma and gallbladder cancer are aggressive cancers with a high disease-specific mortality despite resection. The aim of the present study was to identify predictors of survival after resection.

Methods:

A retrospective review of all patients that underwent radical resection of biliary malignancies was performed. Demographics, elevated CA19-9 (>35 U/ml), treatment and outcome data were collected and compared according to tumour location. Kaplan–Meier survival curves were created and compared using log-rank analysis. Multivariate analysis was undertaken using Cox proportional hazards regression.

Results:

Ninety-one patients with biliary malignancies underwent surgical resection between 1992 and 2007. There were 46 (50.5%) extrahepatic cholangiocarcinomas (EHC), 23 (25.2%) intrahepatic cholangiocarcinomas (IHC) and 22 (24.2%) gallbladder carcinomas (GBC). The median (range) age was 64 (24–92) years. An elevated CA19-9 was recorded in 45 (55%) patients (52% of IHC, 63% of EHC, and 41% of GBC). The overall median (range) survival was 22.5 (0.3–153.3) months. All three groups were similar in terms of age, gender, pre-operative CA 19-9 level, completeness of resection and tumour histopathological characteristics. GBC were associated with the shortest median survival (14.3 months) followed by EHC (24.8 months) and IHC (30.4 months); however, this did not meet statistical significance (P= 0.971). Only elevated pre-operative CA 19-9 level (>35 U/ml) was predictive of poor median survival by univariate (P= 0.003) and multivariate analysis (15.1 months vs. 67.4, P= 0.047).

Conclusions:

Elevated pre-operative CA 19-9 levels were found to be independent predictors of poor survival after attempted resection for biliary tree malignancies. It is recommended that CA19-9 be routinely measured prior resection.     

Is it necessary to perform prophylactic cholecystectomy for asymptomatic subjects with gallbladder polyps and gallstones?

Background and Aims: The purpose of the present study was to determine the clinical characteristics of subjects with gallbladder polyps and cholelithiasis compared with those with gallbladder polyps only. Methods: Between August 1999 and December 2005, 176 subjects with gallbladder polyps and cholelithiasis (study group) by transabdominal ultrasonography performed during a medical check‐up at our institution were recruited and compared with a control group of 185 subjects who had gallbladder polyps only. Results: No significant difference in the mean interval change (delta) of polyp size during the follow‐up period between the study and control groups (0.85 ± 1.39 mm vs 0.84 ± 1.58 mm, respectively, P = 0.927) was noted. A significantly higher proportion (9/176 [5.1%]) of examinees in the study group had attacks of acute cholecystitis compared with the control group (1/185 [0.5%], P < 0.01). By multivariate logistic regression analysis, gallbladder wall thickening on initial ultrasonography (odds ratio, 13.7; 95% confidence interval, 1.1–178.0; P = 0.046) and the interval increase in the size of the gallbladder polyps (odds ratio, 14.7; 95% confidence interval, 1.7–126.9; P = 0.014) were independent risk factors for cholecystectomy. No gallbladder cancer occurred during the follow‐up period. Conclusions: There was no significant difference in delta polyp size between the examinees with gallbladder polyps and cholelithiasis and those with gallbladder polyps only. Hence, a small proportion of subjects with gallbladder polyps and cholelithiasis, such as those with thickened gallbladder walls and an interval increase in the size of the gallbladder polyps are candidates for prophylactic cholecytectomy.     

Post-cholecystectomy biliary strictures: Not always benign

Background:  Post-cholecystectomy malignant biliary obstruction masquerading as benign biliary stricture (BBS) has not been reported in the literature; it presents a diagnostic and management challenge.
Methods:  Of the 349 post-cholecystectomy BBS managed at a tertiary care hospital in northern India between 1989 and 2004, 11 patients were found to have biliary malignancy. Records of these 11 patients were analyzed retrospectively for the purpose of this study.
Results:  Mean age of patients with malignant biliary strictures was significantly higher (52 vs 38 years, P  = 0.000); they were more likely to have jaundice (100% vs 78%, P  = 0.008) and pruritus (82% vs 48%, P  = 0.03). Unlike most patients with BBS referred from elsewhere to us, they had had a smooth postoperative course uncomplicated by bile leak, had a longer cholecystectomy-presentation interval, and were more likely to have high strictures ((Bismuth type III/IV) 91% vs 49%, P  = 0.008).
Conclusions:  Post-cholecystectomy biliary obstruction is not always benign. High bilirubin levels and hilar strictures, especially after an uneventful cholecystectomy, in a middle-aged patient should raise a suspicion of underlying missed malignancy.