Postoperative Complications in Carcinoma Gall Bladder: A Tertiary Care Hospital Experience

Introduction: Gallbladder cancer is more common than any other part of the biliary system. Accounting between 2% and 3% of all cholecystectomies . Aims &Objectives: To analyze different postoperative complications in various stages of operated gall bladder carcinoma. Place and duration of study: Army Liver Transplant Unit (A.L.T.U.) Pak Emirates Military Hospital Rawalpindi (P.E.M.H.), from November 2020 to April 2022. Material & Methods: This cross-sectional descriptive study looked at all patients diagnosed with gallbladder cancer before surgery or who were subsequently found to have benign gallbladder cancer presenting with intra-luminal lesions and localized or diffuse wall thickening amenable to surgical treatment. A sequential sampling method was used to select the patients. A proforma was developed to streamline the data collection process. The patient's gallbladder cancer was staged using the A.J.C.C.'s Eighth Edition staging system, and the degree of complications was classified using the Clavien-Dindo system. Data was entered and analysed using SPSS version 23. Results: A total of 27 patients were included in the study, with male to female ratio of 1:3; and a mean age of 50.1 ± 4.7 years (range 25-70 years). Six patients were in Stage-1 of whom only 1 (3.7%) developed grade – I complication; 9 patients were in Stage-2, out of which 2 (7.4%) developed grade – II complications; 6 patients were in Stage-3, out of which 2 (7.4%) patients developed grade – III and 1 (4.7%) patient developed grade-II postoperative complications. Six (22.2%) were in Stage-4 and underwent curative resection, where no patient developed postoperative complications. Conclusion: Surgery remains a solitary curative option for gall bladder carcinoma, and when patients are selected carefully, postoperative complications after radical surgery are not very high. Moreover, as the stage of the disease increases, so does the complication grade.


INTRODUCTION
Gallbladder cancer is more common than any other part of the biliary system.Gallbladder cancer accounts for between 2% and 3% of all cholecystectomies.Its incidence has grown in the last two decades 1 .The increased incidence of the disease is thought to be attributed to two factors: the general practice of reporting histological findings for all gallbladders removed and the rising popularity of laparoscopic cholecystectomies 2 .People with non-accidental gallbladder cancer are rarely diagnosed with the disease immediately.Surprisingly, even when the severity of the disease is considered, the outcomes are worse than when diseases are discovered by accident.The incidence of gallbladder cancer varies greatly by location 3 .Approximately 22 out of every 100,000 women in northern India are affected.The incidence rate is 11 per 100,000 Indians and Pakistanis in North America 4 .There are few reported cases in Europe (between 0 and 4 per 100,000) 5 .The prognosis for gallbladder carcinoma is poor, with a less than 5% 5-year survival rate.With early detection and surgery based on the disease's stage, 75% of patients diagnosed with cancer can survive for five years 6 .Criteria for stage-adjusted therapy have been published in some countries, but there is a significant deal of diversity in the literature, the standards, and the degree to which people adhere to the guidelines.Patients with pT1 cancer and clean margins after cholecystectomy may not need further treatment.Patients with pT2 or pT3 incidental cancer should have a drastic re-operation to increase their chances of survival.Major surgery, including the removal of the liver and lymph nodes, is an appropriate treatment for cancer 7 for the treatment of gallbladder cancer; the S3 Guidelines suggest either a wedge resection of the gallbladder bed or resection of liver segments 4b and 5 10 .Both of these operations necessitate removing a segment of the gallbladder's bed.Gallbladder cancer patients at stages T2 and T3 commonly receive hepatoduodenal ligament lymphadenectomy after undergoing this treatment 8 .According to the criteria provided by the National Comprehensive Cancer Network, this specific method should be used for carcinomas at stages T1b and above 9 .This study aims to examine data from patients with gallbladder cancer at various stages of the disease and following surgery at our institution.

MATERIAL AND METHODS
This descriptive cross-sectional study was conducted from November 2020 to April 2022, at the Department of General Surgery, Army Liver Transplant Unit (A.L.T.U.) Pak Emirates Military Hospital Rawalpindi.The Hospital's Board of Directors gave the Ethics Review clearance vide reference number A/28/Ec/450/2022.Patients diagnosed with gallbladder carcinoma either before surgery or after surgery for a benign condition were included in the study."Patients whose diagnoses included metastatic disease were not included in the research.The study included 27 participants.Sequential sampling was used to select them.Surgeons, gastroenterologists, diagnostic and interventional radiologists, oncologists, and anesthesiologists worked together to treat each patient.Patient demographic information, surgical details, and post-op complications were recorded on a proforma.Gallbladder cancer in patients were staged using the A.J.C.C. 8 th Edition 7 .Clinical outcomes and case-based compensation following surgery strongly correlated with the C.D.C. grading system.As a result, it is a reliable method for contrasting different surgical procedures 10 .

Statistical Analysis
The data was analyzed using S.P.S.S. 23.Descriptive statistics calculate values like the mean and standard deviation, while qualitative analysis uses metrics like frequency and percentages.

RESULTS
There was a total of 27 patients who were diagnosed with gallbladder cancer, and the ratio of males to females was 1:3.Table-1 illustrates a variety of characteristics of the group under consideration.Six of 27 patients were found to be in T1 disease on histopathology report after routine cholecystectomy.Among these six patients, three were in the T1a category (tumor had invaded lamina propria) for which no further treatment was required, and 3 were in the T1b category (tumor had invaded muscular layer).Out of the patients with T1b disease, three patients had clear cystic duct margin on histopathology report for which radical cholecystectomy plus portal lymph node dissection was done, and one had cystic duct margin involvement on histopathology report for which radical cholecystectomy plus bile duct excision and portal lymphadenectomy was done.Nine patients were found with T2 disease (Tumor enters peri-muscular connective tissue without extension into the serosa).Six individuals had T3 disease (tumor punctures serosa or directly affects the liver or adjacent organs).Five underwent radical cholecystectomy.Two patients' cystic duct margins required bile duct resection.Right hemi hepatectomy was done for hepatic duct involvement.Six individuals with T4 illness exhibited peritoneal metastases on diagnostic laparoscopy and one during laparotomy.

DISCUSSION
Only surgical resection, which removes the affected portion of the gall bladder, can cure gall bladder cancer 1 .Because it is a disease that is so aggressive and potentially fatal, making an early diagnosis is of the utmost significance.Numerous studies have shown that the T.N.M. staging system may give information on survival benefits after surgical procedures 11 .In our research, patients were staged using the T.N.M. classification of gallbladder carcinoma according to the Eighth Edition of the A.J.C.C. guidelines.Simple cholecystectomy is sufficient for T1a tumors, but T1b requires more aggressive treatment 12 .Extended cholecystectomy with regional lymph node dissection and en bloc hepatectomy is recommended for T2 patients 13 .In T3 disease, R0 resection (negative margins and lymph node dissection one level beyond microscopically involved lymph nodes) is associated with improved survival 14 .Our study followed suit.R0 resection for T4 disease is not possible, and 5-year survival is low, so extended radical surgeries were not attempted.Such patients receive adjuvant chemoradiotherapy.In our study, ClavienDindo classification was used to classify postoperative complications.

Primary Tumor
Tx Cannot be evaluated

T0
No indication of a primary tumor This Carcinoma in situ T1a Tumor enters lamina propria T1b Tumor enters the muscular layer

T2
Tumor enters peri-muscular connective tissue without extension into the serosa.

T3
Tumor pierces the serosa (visceral peritoneum) and directly enters the liver or a nearby structure.

T4
A tumor involves the main portal vein or hepatic artery or enters 2 or more organs.

Regional Lymph Nodes
Nx Cannot be evaluated N0 No regional lymph node involved N1 Metastases to 1-3 regional lymph nodes

N2
Metastases to 4  Complications after surgery include hemorrhage, surgical site infection, pneumonia, and bile leakage.
A study on 106 patients operated for gallbladder carcinoma demonstrated surgical site infection in 20.8% of patients, pneumonia in 7.5% and bile leakage in 6.6% of patients 15 .One patient in our study developed a surgical site infection; one developed basal atelectasis, and one developed pneumonia.Bile leaks also occurred in two patients.
No in-hospital mortality occurred in our study.Our results are comparable to those found in literature 16 .
Hospital mortality of up to 7.5% after surgery for gallbladder carcinoma has been reported in a study, with failure to rescue from complications as an important cause of mortality 17 .Rapid diagnosis and prompt management of postoperative complications after intricate surgeries for carcinoma gallbladder is paramount to ensure a speedy recovery and discharge from the hospital 18 .
Compared to any other surgery, surgery on the liver is complex, with risks such as prolonged duration of surgery, intra-operative hemorrhage, massive fluid shifts, and hypotension, along with postoperative complications such as coagulopathy or bleeding, pulmonary complications, bile leaks, liver failure 19 .All of these present challenges to the operating team.Enhanced recovery after surgery (ERAS) program has been found to be safe and effective in reducing postoperative complications in patients undergoing hepatobiliary surgery 20 .It has been found to enhance patient recovery and reduce hospital stays without increasing treatment costs or complications 21 .ERAS program involves various pre-operative, intra-operative and postoperative elements 22 .Preoperative elements include minimal fasting, no mechanical bowel preparation, pre-operative carbohydrate load and venous thromboembolism prophylaxis.Intra-operative elements include antimicrobial prophylaxis, skin preparation, use of balanced crystalloids, normothermia and glycemic control.Postoperative elements include multimodal analgesia, early mobilization and early oral intake 23 .ERAS program should be implemented in true letter and spirit in our setup to reduce postoperative complications, as it has been proven its utility in multiple studies 23 .

Grade I
Any nonconformity from usual postoperative recovery without requiring pharmacological, surgical, endoscopic or radiological interventions.
Wound infections opened at the bedside are also included.

Grade II
Pharmacological treatment with drugs other than those mentioned for grade I complications.

Table - 3: Postoperative Complications according to Clavien Dindo Classification in different stages of Carcinoma (n=6).
Table-2 shows A.J.C.C. 8th edition stage-wise patient distribution.Out of these 27 patients studied, 6 patients developed postoperative complications.According to Clavien Dindo's classification of different stages of the carcinoma gall bladder, postoperative complications were studied (Table-3).Among stage I patients, one developed grade-complication (superficial surgical wound infection).Among stage II patients, two patients developed grade -II complications.One developed basal atelectasis, and the other had a minor bile leak.Among stage 3 patients, two developed grade-III complications and one developed grade-II complications.One patient had a biloma, which needed image-guided drainage.And one patient developed a postoperative hemorrhage, which required laparotomy.Grade -II complication patient had developed pneumonia.
*Where the grade is according to ClavienDindo classification and stage according to A.J.C.C. 8th edition.

Table 4
presents the T.N.M. classification according to the A.J.C.C.'s eighth edition.