Prevalence and predictors of postcholecystectomy syndrome in Nepalese patients after 1 week of laparoscopic cholecystectomy: a cross-sectional study

Postcholecystectomy syndrome (PCS) is persistent distressing symptoms which develops following a laparoscopic cholecystectomy (LC); in cases when the condition is severe, readmission may be necessary. However, research on the prevalence of PCS and potential factors associated with PCS in Nepalese patients is still limited. An observational point-prevalence, correlational predictive cross-sectional study was conducted to determine the prevalence of PCS and examine what predicting factors including preoperative anxiety, preoperative dyspepsia, smoking, alcohol consumption, and duration of preoperative symptoms are associated with PCS. A total of 127 eligible Nepalese patients who came for follow-up after 1 week of LC at outpatient department of surgery in one single university hospital, Kathmandu, Nepal, were recruited. A set of questionnaires consisting participants' information record form, Hospital Anxiety and Depression Scale (HADS), Leeds Dyspepsia Questionnaires (LDQ), Fagerstrom Test for Nicotine Dependence (FTND), and Alcohol Use Disorder Identification Test (AUDIT) was administered for data collection. The associations between influential factors and PCS were analyzed using Binary logistic regression. 43.3% of participants reported PCS after 1 week of surgery. The findings from logistic regression analysis affirmed that the patients with preoperative anxiety (OR = 6.38, 95%CI = 2.07–19.67, p < 0.01) and moderate to severe dyspepsia (OR = 4.01, 95%CI = 1.34–12.02, p < 0.05) held the likelihood to report PCS 6.38 and 4.01 times, respectively, greater than others. The implications from study results are that screening of anxiety and patients’ tailored interventions to reduce anxiety should be implemented preoperatively. An appropriate health education about persistence of PCS and self-management should be provided to those postoperative patients.


Participant selection and setting
All the patients, aged 18 years and above, were undergone LC and came for a follow up visit after 1 week of surgery at the surgical department of a single University Hospital, in Nepal.Sample size of 127 was calculated using G* power 34 analysis which is based on the predictive power of anxiety by Merten et al. 25 A total sample of 127 patients was recruited according to inclusion criteria; (1) being undergone elective LC, (2) diagnosed with cholelithiasis, cholecystolithiasis, choledocolithiasis, post endoscopic retrograde cholangiopancreatography (ERCP) and cholecystitis, (3) having ASA grade I and II, and (4) GP-COG 35 equal to 9 for the age of 60 years and above.While patients who had previous abdominal surgery, carcinoma, pregnancy, and history of any psychiatric illness or taking any psychotic drugs were excluded from the study.

Data collection and instruments
A set of questionnaires consisting participants' information record form, Hospital Anxiety and Depression Scale (HADS) 36 , Leeds Dyspepsia Questionnaires (LDQ) 37 , and Fagerstrom Test for Nicotine Dependence (FTND) 38 and Alcohol Use Disorder Identification Test (AUDIT) 39 was applied for data collection.Approval from the original author has been received before using the above instruments.The translated Nepali version of HADS, FTND and GP COG was employed whereas LDQ and AUDIT were back translated by the researcher, language expert, and surgeon and nurse expert.
HADS is composed of 14 items each 7 items for anxiety sub-scale (HADS A) and depression subscale (HADS D) which is assessed separately.Each item in the scale is rated on 4 points Likert scale 0-3 where 3 indicate the maximum severity and the scores are summed 36 .The total scores range from 0 to 21 for each sub-scale and can interpret as no cases (0-7), doubtful cases (8-10), and cases (11-21).Back-translated LDQ, Nepali version, is 8 items questionnaire which consists of 2 stems for frequency and severity of dyspeptic symptoms.LDQ has a score ranging from 0 to 40 and contained questions on epigastric pain, retrosternal pain, regurgitation, nausea, vomiting, belching, early satiety, and dysphagia 37 .The frequency of the first five questions was used to determine the presence of dyspepsia and all 8 questions were required to measure a severity.For the participants who had history of smoking and alcohol consumption, FTND and AUDIT was used 38,39 .
All participants completed each questionnaire after giving an informed consent.For participants who could read Nepali, each questionnaire was self-administered; for ones who could not read, the researcher read the questionnaire out to them.This study was reported concerning the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement 40 .

Statistical analysis
Bivariate analyses used with a Chi-squared test and multiple logistic regression were conducted to compare two outcome groups (cases vs non-cases of PCS) and identify the associated factors for PCS.The variables for predicting factors including preoperative anxiety, preoperative dyspepsia, smoking, alcohol consumption, and duration of preoperative symptoms were analyzed in relation to the occurrence of PCS.The Hosmer Lemeshow and the Nagelkerke R 2 tests were reported for the logistic regression analysis.SPSS statistics version 25.0 for Windows (IBM Corp., Armonk, NY, USA) was utilized for statistical analysis of all data.

Ethical considerations
After the ethical approval from Institutional Review Board of Faculty of Nursing (NS-IRB) (COA No. IRB-NS2021/599.0802),Mahidol University, Thailand, and Institutional Review Board of Kathmandu University, School of Medical Sciences, Dhulikhel Hospital (IRC KUSMS Approval No 28/2021), Nepal, a data collection was started.Written informed consent was obtained from each participant before enrolling in the study.

Characteristics of participants
As Table 1, this study showed that 43.3% of participants had PCS after 1 week of LC.Large proportions of participants were female (72.4%).Nearly half of participants (48%) aged 18-40 with mean age of 42.88 ± 13.12 years.Almost half of the female participants (46.7%) had PCS after 1 week of LC.Likewise, more than half of the participants (54.5%) aged more than 60 developed PCS.The mean age of participants who had PCS was 44.93 ± 13.81 years.
Out of 127 participants, 39.4% had one or more than one underlying disease.Among them, half the participants (52%) had hypertension.Secondly, one-third of the participants (30%) had Diabetes Mellitus, and only 6% had cardiovascular diseases.Moreover, 73.3% of participants who had Diabetes Mellitus developed PCS to the same degree as 66.7% of participants with cardiovascular disease and other diseases.
As Table 2, preoperative anxiety and depression were assessed using HADS.The mean preoperative anxiety score was 7.08 ± 4.34.The participants who scored 11-21 (case) were 18.9%.However, a larger proportion of participants (79.2%) who scored 11 or more experienced PCS.
Preoperative dyspepsia was assessed by the Leeds Dyspepsia Questionnaire.The mean preoperative dyspepsia score was 6.34 ± 6.37.The result showed that 41.7% of participants had very mild to mild dyspepsia, followed by 30% of participants had moderate to severe dyspepsia, and 28.3% of participants had no preoperative dyspepsia.www.nature.com/scientificreports/More than half of the participants (63.2%) with moderate to severe dyspepsia had PCS, followed by 41.5% of participants with very mild to mild dyspepsia.In this study, majority of participants (77.2%) were non-smoker, whereas 22.8% were smoker (n = 22).The result presented that a proportion of participants who had PCS and ones who had no PCS was almost same.Likewise, third-fourth of the participants (75.6%) did not consume alcohol.Almost equal proportion of participants who consumed alcohol and did not consume alcohol had PCS as 41.9% and 43.8%, respectively.This present study pointed out that the mean preoperative symptom duration was 16.64 ± 27.30 months.Nearly half of the participants (48.5%) having symptoms duration more or equal to 12 months experienced PCS.

Associations between the studied predicting factors and PCS
Results from Chi-square analysis reported that only two studied variables were statistical significantly associated with PCS in this study.These factors include preoperative anxiety (χ 2 = 16.17,p < 0.001), and preoperative dyspepsia (χ 2 = 11.08,p < 0.01).Participants, who were cases, were more likely to develop PCS (79.2%).Similarly, more than half of participants with moderate to severe dyspepsia were more likely to have PCS (63.2%).The results of Chi-square test is shown in Table 3.
As Table 4, to identify the predictors of the PCS among patients after 1 week of LC in a university hospital in Nepal, a binary logistic regression test was employed.The study findings revealed that having anxiety preoperatively (Cases) (OR = 6.38, 95%CI = 2.07-19.67,p < 0.01) and having moderate to severe dyspepsia (OR = 4.01, 95%CI = 1.34-12.02,p < 0.05) were more likely to experience PCS.

Discussion
In this present study, the PCS was determined by the attending surgeon at the time of follow-up after 1 week of LC according to the definition of PCS, history taking, and physical examination.The prevalence of PCS in this study was 43.3% which is higher than other previous studies 26,41,42 .Nepalese participants who had PCS were asked for follow-up after one month in the outpatient department, and whether symptoms persisted, they would be taken for another treatment plan.The finding of this current study was similar to Angeline and Lalisang's study that noted the prevalence of PCS in Indonesia to be 45.5%, but in the different periods from soon after surgery to 18 months after surgery 27 .According to the study of Kouloura et al. 21, the onset of symptoms in PCS occurred from 2 days to 25 years after LC.Only a few studies had reported the prevalence of PCS after 1 week of cholecystectomy 15 .Otherwise, the prevalence of PCS in our study was quite smaller than Arora et al. 14 which reported the PCS of 58% after 1 week, 39.1% in 1 month, 23.2% in 3 months, and 13% in 6 months.The other study reported a lower prevalence of 17.1% when followed up after one month of LC 41 .Another study found that 23% of study participants had  persisted preoperative symptoms after 4 months of surgery 26 .Likewise, a study reported the prevalence to be 16.66% after 3-10 months after surgery 42 .Similar to several reports, another study noted 19.8% of PCS where the exact follow up period after surgery was not mentioned 43 .Most of those aforementioned studies had a lower rate of PCS when compared to the present study.As we discussed the prevalence of PCS was higher when followed up after 1-week whereas in other studies where the followed-up period was longer.In a study, they reported decreasing prevalence of PCS as an increase in time duration 14 .This might be the reason why the current study had a higher rate of PCS as participants were followed up only after 1 week of surgery.Also, due to the alteration of bile flow after the removal of the gallbladder, it resulted in various gastrointestinal symptoms like bloating, belching, flatulence, etc.The body needed to adopt the physiological changes and patients might have those symptoms during adaptation 7,16 .This might be another reason why this study had a higher prevalence of PCS.
Corresponding with the previous study reported 38.75% of patients had preoperative anxiety that underwent LC.A main reason for preoperative anxiety was found to be fear of post-operative pain and of anesthesia 44 .In this current study, 18.9% of participants had preoperative anxiety.This result was in line with the previous study reported high trait anxiety as the only predictor of persistence of biliary symptoms 6 weeks after cholecystectomy 12 .However, there was a difference in measurement tools to measure the preoperative anxiety in a previous study and current study, the results were congruent.The previous study reported there was the presence of some sort of anxiety before surgery and how psychological distress added to the pathophysiology of PCS.Therefore, the result of this study that preoperative anxiety as a predictor of PCS could be explained.
Regarding the reviewed literatures, there were no recent researches that studied preoperative dyspepsia as a predicting factor of PCS.However, this result can be in line with a decade-old 25 where the researcher proposed preoperative reports of dyspeptic symptoms to predict new dyspeptic symptoms after 6 months.Even though the measurement of preoperative dyspepsia and time duration when the patients were followed up were different from current study.However, our results were similar in that preoperative dyspepsia could predict the PCS.
This result could be supported insight into the pathophysiology of PCS and dyspepsia.There were various causes of dyspepsia including alteration of gastric motility, visceral hypersensitivity, H. pylori infection, psychological factors, etc 45 .An absence of gall bladder after surgery results in a continuous drainage of hepatic bile to the duodenum which causes rapid enterohepatic bile cycling and surplus passage of bile juice into the duodenum 16 .This causes an increase in duodenal gastric reflux and leads to the sphincter of Oddi incompetence which further added alteration of gastric motility 16,29 .Moreover, the bile duct needed 1-2 weeks to recover from dilatation after surgery.This might be a reason why patients, who had preoperative dyspepsia, might develop new symptoms of dyspepsia after surgery 6,18 .
Additionally, preoperative dyspepsia is one of the significant predictors for PCS.Nurses should preoperatively screen the patients who have a treatment plan of LC for its dyspepsia level of severity and manage properly.An individual-tailored patient's education on how to manage dyspepsia and persistent dyspeptic symptoms after surgery should be intervened.As a preoperative anxiety was one of the statistically significant predictors of PCS, evaluating all patients who were planned for LC and finding out its cause will help managing occurred anxiety suitably before getting an operation.An appropriate health education about possibility of having persistent PCS should be explained to preoperative patients with LC, and what self-management of symptoms should be followed.

Conclusions
To summarize, this study revealed that nearly half of patients with LC reported PCS.Postoperative female patients whose age greater than 60 years and having underlying disease are more likely to suffer PCS than other groups.The preoperative anxiety and preoperative dyspepsia were significant predictors of PCS.The patients with preoperative anxiety and moderate to severe dyspepsia held the likelihood to experience PCS 6.38 and 4.01 times, respectively, greater than others.Based on these results, screening and prompt management of preoperative anxiety and dyspepsia as to minimize risk for PCS along with specific patient's education regarding PCS information in patients planned for LC should be initiated.A proper postoperative follow-up and monitoring of PCS should be provided accordingly.

Strength of the study
Since it is limited data of PCS and its predictors in Nepali context, this study revealed the prevalence of PCS after 1 week of LC is 43.3% which can be used as the base for further study.Results of this study can be used to identify a risk group and provide appropriate tailored education as to manage existing symptoms.This study also indicated an importance of monitoring the patients following LC for symptomatic outcomes at follow up time.

Limitation of the study
The diagnosis of PCS is only preliminary diagnosis, yet it would not be definitive.This study was conducted in a single setting, university hospital, in Nepal, and only included patients who came for 1 week follow-up, thus the results may not be generalized.A nature of cross-sectional study design would not acknowledge to measure changes over time condition, which was impractical to infer causality and comparison of interest outcomes.The repeated measure case-control study would be a challenge for a future research. https://doi.org/10.1038/s41598-024-55625-1

Table 1 .
Frequency, percentage, mean, and standard deviation of participant characteristics and PCS (n = 127).

Table 2 .
Frequency, percentage and standard deviation of preoperative anxiety using HADS and preoperative dyspepsia, and PCS (n = 127).