It has been demonstrated that laparoscopy can be performed safely during any trimester of pregnancy with minimal morbidity to the fetus and mother [79–91] [LoE2-LoE3-LoE4].

The significant morbidity and mortality associated with untreated benign gallbladder diseases in the gravid patient favors surgical treatment [79, 84, 87–89, 92–94] [LoE2-LoE3-LoE4].

LC is the treatment of choice in the pregnant patient with benign gallbladder diseases [79, 95] [LoE2-LoE3].

Patients with symptomatic gallstones who were treated conservatively have shown a 92 % recurrence rate when symptoms were present in the first trimester, 64 % when symptoms were present in the second trimester, and 44 % when symptoms were present in the third trimester. This data support an early surgical approach to gravid patients with symptomatic gallstones [79, 95] [LoE2-LoE3].

The delay in surgical management results in increased rates of hospitalizations, spontaneous abortions, preterm labor, and preterm delivery compared to those undergoing cholecystectomy [79, 93, 96] [LoE2-LoE3-LoE4]. Nonoperative management of symptomatic gallstones in gravid patients results in recurrent symptoms in more than 50 % of patients, and 23 % develop acute cholecystitis or gallstone pancreatitis [79, 84, 97] [LoE2-LoE3-LoE5]. Gallstone pancreatitis results in fetal loss in 10–60 % of pregnant patients [79, 89] [LoE2-LoE3]. Gravid patients candidate to LC should be placed in the left lateral recumbent position to minimize compression of the vena cava and the aorta [79, 92] [LoE2-LoE5].

There has been much debate regarding abdominal access in the pregnant patient with preferences toward either a Hasson technique or Veress needle. Because the intra-abdominal domain is altered during the second and third trimester, initially accessing the abdomen to create the pneumoperitoneum via a subcostal approach has been recommended. If the site of initial abdominal access is adjusted according to fundal height and the abdominal wall is elevated during insertion, both the Hasson technique and Veress needle can be safely and effectively used [79, 82, 84, 89, 95, 98] [LoE2-LoE3-LoE4].

Life expectancy continues to increase in Western countries and the incidence of gallstones increases parallel with age [99] [LoE4]. Gallbladder disease is the most common indication for abdominal surgery in the elderly and therefore cholecystectomy is the most commonly performed surgical procedure [100, 101] [LoE4].

All examined studies demonstrated that LC is indicated for elderly patients with uncomplicated gallbladder stone disease, as results are better than those obtained with open cholecystectomy (OC) regarding morbidity, length of surgery, and mean postoperative hospitalization with more discharges to home [102–107] [LoE2-LoE3-LoE4]. Nevertheless Tucker et al. in a recent case-match study, based on American College of Surgeons National Surgical Quality Improvement Program database, stated that elderly patients were more likely to undergo OC compared to younger age group, concluding that LC is safe but underused in the elderly [108] [LoE3].

LC in older patients is associated with increased rates of conversion to laparotomy, longer operation time, longer hospital stay, and increased rates of operative complications, such as bile duct injury and hemorrhage, than when performed in younger patients [109, 110] [LoE2-LoE4]. These differences are probably due to the evidence that elderly patients are more likely than the younger ones to have had prior abdominal upper surgery or longstanding gallstone disease with chronic inflammatory changes and adhesions in the right upper quadrant. Moreover, elderly experience a high incidence of choledocholithiasis and gallstone pancreatitis and a higher frequency and severity of associated cardiopulmonary disease [101, 111] [LoE4].

Kim et al. stated that perioperative outcomes in the elderly seem to be influenced by the severity of gallbladder disease, and not by chronologic age [100] [LoE4].

On the basis of these observations, early elective LC should be encouraged in symptomatic elderly patients before the development of complicated cholelithiasis [100, 101, 112] [LoE4]. Such approach may serve ultimately to lower conversion to open cholecystectomy (OC), reduce the incidence of acute presentations with common bile duct stones, and possibly lower complications and mortality [101] [LoE4].

In conclusion LC can be performed with acceptable morbidity in extremely elderly, like octogenarians, with complicated gallstone disease, although it should be considered and encouraged also for this age group of patients when gallstone disease is still uncomplicated, because early treatment could further improve outcomes. However octogenarians have a higher rate of conversion to OC, more complications, and higher mortality rates [99–101, 112–114] [LoE4].

The treatment and surveillance of GPL is still controversial as a result of the lack of RCTs [115] [LoE2]. There is no evidence from randomized clinical trials to either recommend surgery or not for patients with GPL smaller than 10 mm [116] [LoE2].

For patients with GPL associated with pain, nonrandomized trials have shown that LC offers good pain relief in more than 90 % of the cases [117] [LoE4]. The primary goal in GPL management is to prevent gallbladder carcinoma, even though it is a rare condition [118] [LoE2].

Any surgeon has to balance the risk of malignancy (ranging between 45 and 67 %) in polyps between 10 and 15 mm in size [119–122] [LoE3-LoE4] and the risks associated with LC.

The ultrasound (US) evidence of multiple polyps per se is not considered an indication for surgery [115] [LoE2].

In patients with age ≥60 years, sessile polyp morphology, and polyp size ≥10 mm, a generous approach to endoscopic ultrasound (EUS) or multislide CT for accurate characterization should be advised [118] [LoE2].

Authors indicate as risk factors in patients with gallbladder polyps the following characteristics (Table 3.2) [118–130] [LoE2-LoE3-LoE4]:

If there are no signs of malignancy, for polyps 6–9 mm in diameter, a US examination is recommended after 6 months. If the US examination does not show any significant changes, a new US examination is recommended after 12 months. No further follow-up in case of stable lesion is recommended [118] [LoE2].

GPL smaller than 6 mm do not require follow-up in the absence of suspicion of malignancy [118, 131] [LoE2-LoE4].

A GPL greater than 18 mm has a high likelihood of gallbladder cancer: open cholecystectomy, partial liver resection, and lymph node dissection are advised [120] [LoE4].

Based on the literature review, we propose the following flowchart for gallbladder polypoid lesions management (see Fig. 3.1).

Cholelithiasis in patients with cirrhosis occurs twice as often as in general population. Despite cholecystectomy is the most frequently performed surgical procedure for patients with liver cirrhosis, there are few studies about laparoscopic cholecystectomy (LC) in those patients. The studies are small, heterogeneous in design, and include almost exclusively patients with Child-Pugh class A and B. There are poor data about LC outcome in Child-Pugh class C [132] [LoE1].

However, three systematic reviews (including a total of 4,211 patients) and four meta-analysis of RCTs (including a total of 1,138 patients) comparing outcomes of open cholecystectomy (OC) versus LC for symptomatic cholelithiasis in Child-Pugh A or B cirrhotic patients show fewer overall postoperative complications, a shorter hospital stay, shorter operative time, and faster resume of a regular diet for the LC group than for the OC group [132–139] [LoE1-LoE2-LoE3].

Because of the high risk of liver failure and heavy hemorrhage in Child-Pugh C patients, the indications for surgery in this subset of cirrhotic patients should be evaluated very carefully and surgery avoided unless clearly indicated [140] [LoE4]. In such patients cholecystostomy or percutaneous drainage of the gallbladder as alternative options should be considered [140] [LoE4].

The severity of cirrhosis is a major determinant in the decision-making process on the optimal approach [135] [LoE2]. Both Child-Pugh and MELD scores were used to predict postoperative morbidity and mortality in patients with liver cirrhosis [134] [LoE1]. Review of the literature showed that cirrhotic patients who undergo non-hepatic surgery exhibit postoperative morbidity and mortality rates strongly related with the severity of cirrhosis and the nature of the surgical procedure [134] [LoE1].

The increased risk for a major complication, however, demands more attention than usual.

The morbidity rates for OC in patients with cirrhosis are reported to be between 30 and 35 % while for LC between 13 and 33 %. However, mortality after OC varied between 0 and 7.7 % [134, 135, 139, 141] [LoE1-LoE2-LoE3].

Some studies report a 3.4-fold higher risk of mortality for cirrhotic patients undergoing cholecystectomy when compared to non-cirrhotic patients [134, 142] [LoE1-LoE3].

Long-term complications after cholecystectomy for cirrhotic patients, such as abdominal wall hernias and adhesions, are not assessed in literature, but it is demonstrated that they occur less frequently after laparoscopic cholecystectomy than open cholecystectomy in patients with a non-cirrhotic liver. In the hypothesis of future surgery, for example, liver transplantation, cirrhotic patients could even take greater advantage of this fact [133] [LoE1].

Acalculous gallbladder disease represents a clinical entity which is not clearly defined and incorporates chronic and/or acute inflammation, gallbladder and/or biliary dyskinesia, intrinsic motility disorders, and functional disorders of biliary flow [143–146] [LoE4]. Nonetheless, gallbladder dyskinesia, in the absence of gallstones or polyps, is a challenging clinical entity in laparoscopic era.

Gallbladder dyskinesia is a motility disorder of the gallbladder (acalculous) associated with intermittent right upper quadrant pain (classic symptoms) [147] [LoE4]. More recently Corrazziari and Cotton published a flowchart to assess the diagnostic criteria and treatment options [148] [LoE4].

The incidence of negative US examination in patients complaining about biliary pain differs between the two sexes, ranging from 7.6 % in males to 20.7 % in females [149] [LoE5].

There are three hot topics concerning the management of this clinical entity:

Preoperative diagnostic evaluation should include serial dynamic ultrasonography, upper ultrasound-endoscopy (to rule out microlithiasis), and dynamic cholescintigraphy [144, 150–153] [LoE3-LoE4].

CCK-HIDA scintigraphy is considered by many authors as the first specific test (high specificity) for gallbladder dyskinesia [153, 154] [LoE4]. Its increasing utilization coupled with decreasing utilization of other preoperative evaluation methods may indicate increasing physician awareness of the disease and appropriateness of the CCK-HIDA scintigraphy as a predictor of postoperative success after cholecystectomy [143, 150, 153] [LoE4]. In 2003 DiBaise et al. [155] [LoE3] in their systematic review concluded that the quality evidence of the 23 papers selected was lacking precluding a definitive recommendation regarding its use. In 2010 the Rome Committee stated that CCK-HIDA scintigraphy is not a standardized test and may be conducted differently in different institutions. Moreover the extent to which the results predict the surgical outcome remains controversial. Finally, reproduction of pain on injection of cholecystokinin (CCK) has been considered to indicate gallbladder motor disorder, but this is not a reliable predictor of favorable surgical outcome. Recently an evidence-based review [156] [LoE3] concludes that despite the widespread acceptance of CCK-HIDE provocative test and its standardization, high-quality data indicating efficacy of cholecystectomy in the treatment of this condition are still lacking.

Clinical signs and symptoms still remain the most important criteria for some surgeons for patient selection to surgical treatment [152–170] [LoE3-LoE4-LoE5]. While few nonrandomized clinical studies have demonstrated a discriminatory ability of the impaired gallbladder ejection fraction (<35 %) in predicting the symptoms relief after cholecystectomy [152–154, 157, 158, 160–162] [LoE3-LoE4-LoE5], other published studies have not confirmed this [155, 163] [LoE3]. Carr et al. reported the results of a prospective nonrandomized concurrent cohort study on the treatment of gallbladder dyskinesia (defined as negative ultrasound examination and ejection fraction <35 % after CCK stimulation) based upon typical and atypical biliary symptoms. This study demonstrated that classic biliary symptoms are more predictive of success after cholecystectomy in patients with gallbladder dyskinesia than are atypical symptoms. The resolution of symptoms in the “classic symptom group” was 97 % versus 57 % in the “atypical symptom group.” The ejection fraction was not significantly different between the two groups [164] [LoE4]. Actually 5–27 % of gallbladder dyskinesia cases are approached by LC (majority in females) [149, 165, 166] [LoE3-LoE4-LoE5].

LC alleviates symptoms in about 50 % of unselected patients with chronic acalculous cholecystitis/biliary dyskinesia with minimal morbidity, and patients who suffered symptoms for a longer period of time preoperatively were more likely to be satisfied [149, 151, 167] [LoE4-LoE5].

In 2005 Ponsky et al. [168] [LoE3] included in their systematic review and meta-analysis of 5 studies (275 patients, 1963–2003) reporting data and follow-up on efficacy of cholecystectomy versus no treatment in patients with gallbladder dyskinesia. The meta-analysis showed 98 % symptomatic relief in cholecystectomy-treated group versus 32 % in the control group (no treatment). However, the analysis was lacking in high-quality paper. Pathologic examination of the removed gallbladder demonstrates acalculous chronic cholecystitis in 67–95 % [158] [LoE5].

In 2009 Gurusamy et al. [169] [LoE3] underlined in the conclusions of their Cochrane Review that the evidence for benefits and harms of cholecystectomy in the treatment of gallbladder dyskinesia is based on a single small randomized controlled clinical trial (21 patients, 11 open cholecystectomy vs. control) being therefore at risk of bias. Randomized clinical trial in laparoscopic era is advocated.

In quality of life terms, the usefulness of laparoscopic cholecystectomy is similar in patients with calculous or acalculous gallbladder disease, thus making its surgical indication reasonable [152] [LoE3]. LC should be offered as elective treatment to those patients who understand the magnitude and potential success and failure of LC.

In conclusion, the diagnosis of gallbladder dyskinesia is based mainly on clinical signs and symptoms with typical biliary pain, especially after meals, negative serial US examinations and EUS and a positive CCK stimulating test. The CCK-HIDA scintigraphy seems to be predictive for gallbladder dyskinesia if ejection fraction is <35 %, but it is not predictive for surgical outcomes. Both patients presenting with typical and atypical biliary symptoms will benefit from cholecystectomy, but there is greater benefit for patients with typical biliary symptoms, regardless of the entity of reduced ejection fraction. In this view, LC should be proposed to patients with gallbladder dyskinesia suffering from typical symptoms. A wait and see policy is recommended for patients with atypical symptoms. But if symptoms persist, they can be sent to LC after a careful interview, explaining pros and cons and the insecure success and deciding together with the physician.