Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis.

BACKGROUND: Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. AIM: To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. METHODS: A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. RESULTS: Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). CONCLUSION: There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Lessons learnt from 1300 consecutive gallbladder cancer surgeries: Evolving role of peri-operative chemotherapy in the treatment paradigm.

BACKGROUND: Level I evidence for multi-modality management of gallbladder cancers (GBC) is evolving. METHODS: Prospectively maintained operative GBC database of 1307 patients (year 2010-2019) was analysed to study the impact of peri-operative chemotherapy (PCT) on survival outcomes. RESULTS: 1040 patients had pathologically confirmed GBC. Stage distribution showed: Stage I(85,8.2%), II(247,23.8%), III(460,44.2%), IV(248, 23.8%). PCT was used as follows: in stage II, 164 patients received adjuvant chemotherapy(ACT); in stage III, ACT was given to 444 patients, either operated upfront(244 patients) or after neoadjuvant chemotherapy (NACT)(216 patients); in stage IV, 32 patients (11 received NACT) underwent radical surgery followed by ACT and 216 patients had inoperable disease (77 received NACT) upon exploration. With a median follow-up of 30 months, the 3-year OS for stage I, II and III was 94.1%, 82.6% and 48.2% respectively. Corresponding DFS was 93.8%, 67.3% and 38.3%. Upon reassessment for surgery after NACT (n = 332), patients who underwent radical surgery (n = 235) had superior OS (p = 0.000) and DFS (p = 0.000) in comparison to those who had inoperable disease (n = 97). Amongst stage III and IV patients with operable disease (n = 492), those who were operated upfront (n = 238) had equivalent survival as those operated after NACT (n = 254). This was also confirmed by a 1:1 propensity matched analysis (118 patients each), matching for T and N stage. CONCLUSION: The role of peri-operative chemotherapy in management of GBC is evolving. While the role of NACT for locally advanced GBC is unsettled and merits testing prospectively, it helps in selection of patients with favourable disease biology for radical surgery.

Cowden Syndrome With Gall Bladder Polyps and Incidental Gall Bladder Carcinoma.

Cowden syndrome is an uncommon autosomal dominant disorder characterized by multiple hamartomas in various tissues. It is associated with germline mutation in the phosphatase and tensin homolog (PTEN) gene. It has an increased risk of malignancies of various organs (commonly breast, thyroid, and endometrium) and benign overgrowth of tissues like skin, colon, and thyroid. Here, we present a case of Cowden syndrome in a middle-aged female who presented with acute cholecystitis with gall bladder polyps along with intestinal polyps. She underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA) with diversion ileostomy and cholecystectomy, which was further proceeded to completion of radical cholecystectomy based on the final histopathology report as incidental gall bladder carcinoma. To the best of our knowledge, this association is seen for the first time in the literature. In Cowden syndrome, patients should be counseled for regular follow-up and instructed to be aware of the signs and symptoms of different types of cancers with higher incidence.

A rare occurrence of a poorly differentiated large cell neuroendocrine carcinoma of the gallbladder: A case report and review of the literature.

INTRODUCTION: Neuroendocrine carcinoma (NEC) of the gallbladder is a rare entity with much of the surgical strategy and management mirroring that of adenocarcinoma of the gallbladder. In contrast to gallbladder adenocarcinoma, however, it tends to be a more aggressive and lethal malignancy associated with a short survival after the time of diagnosis. Furthermore, due to its rarity, there are no consensus guidelines for its management. PRESENTATION OF CASE: We present the case of a 73-year-old female who presented with acute cholecystitis and was found to have a poorly differentiated large cell NEC of the gallbladder after laparoscopic cholecystectomy. She was treated with adjuvant chemotherapy and has shown no evidence of cancer recurrence on three-year follow up. DISCUSSION: Surgical resection is the cornerstone of curative treatment for gallbladder NEC. Management may include simple cholecystectomy, extended cholecystectomy, radical cholecystectomy, or palliative cholecystectomy. It is unclear whether lymphadenectomy confers a survival benefit. Adjuvant chemotherapy with platinum-based regimens, on the other hand, has been associated with increased survival rates. Radiation, immunotherapy, somatostatin analogs and targeted therapy have also been used for treatment. CONCLUSION: NEC of the gallbladder is extremely rare, aggressive, and carries a dismal prognosis. Further studies are needed to develop the optimal treatment approach to increase survival rates and establish best practices to manage these patients.

Clinical presentation and management modalities of gallbladder cancer in Sudan: A single-center study.

Background and Aim: Gallbladder cancer (GBC) is a rare and highly aggressive malignancy characterized by late presentation of nonspecific symptoms, poor curability, and high mortality. The gold standard for effective treatment depends on early detection and surgical excision. Hence, the aim of this study was to determine the patterns of clinical presentation and management modalities to reach excellent practice. Methods: A retrospective study was conducted during the period from May 2021 to April 2022 at Ibn Sina specialized hospital, Khartoum, Sudan, on 50 patients with GBC who underwent a preoperative clinical and radiological evaluation to enable the use of appropriate surgical and oncological approaches. Results: GBC was more prevalent in females in this series where all had GBC (68%), in the ratio 2:1. Distribution of patients according to age ranged between 61 and 75 years, representing 44% of patients. Abdominal pain, nausea, and vomiting were present in 40% of patients. Fifty-six percent of patients resided in urban areas. Transabdominal ultrasound (TUS) with CT scan diagnosed GBC in 54% of patients. GBC was metastatic (stage IV) in 52% of patients. Based on preoperative decision by a multidisciplinary team (MDT), 62% of patients had palliative nonsurgical oncological treatment. Histopathological analysis of the resected GBC showed adenocarcinoma in 74% of cases. The inoperable patients (42%) were treated palliativelly with endoscopic retrograde cholangiopancreatography/systemic chemotherapy. Finally, the overall mortality rate was 56%. Conclusions: Accurate early clinical diagnosis and advanced radiological modalities with curative surgical approaches including clear surgical resection margins and systemic oncological therapies will potentially help in improving GBC survival outcomes.

Adenocarcinoma de vesícula biliar: un caso de presentación temprana / Gallbladder adenocarcinoma: an early-stage case

El cáncer de la vesícula biliar es una enfermedad rara, con una incidencia mundial de 2 casos por cada 100 000 individuos con un pronóstico desfavorable. Con el aumento de colecistectomías por causas benignas, se ha incrementado la detección incidental de neoplasias vesiculares en las piezas quirúrgicas, siendo este el método diagnóstico más frecuente, generando retrasos en el manejo y requiriendo reintervenciones extensas. Debido a lo anterior, se resalta la importancia de un diagnóstico temprano preoperatorio, con el objetivo de ofrecer un tratamiento quirúrgico potencialmente curativo. Se presenta el caso de un paciente masculino de 72 años con un cuadro intermitente de dolor abdominal y pérdida de peso de un año de evolución, el cual fue diagnosticado con cáncer vesicular en etapa temprana y sometido a una colecistectomía laparoscópica extendida con linfadenectomía y hepatectomía parcial con una evolución a 6 meses sin complicaciones y bajo un protocolo de vigilancia periódica.

Gallbladder cancer is a rare disease, accounting a global incidence of 2 cases per 100 000 individuals with an unfavorable prognosis. The rise in cholecystectomies for benign causes has increased an incidental detection of vesicular neoplasms in the surgical specimens, being the main diagnostic method, therefore it generated delay in the management, requiring extensive re-interventions. It is important to improve early preoperative diagnosis, with the aim of offering a potentially curative surgical treatment. We present a case of a 72-year-old male with intermittent abdominal pain and weight loss of one year of evolution, who was diagnosed with early stage gallbladder cancer and underwent an extended laparoscopic cholecystectomy with lymphadenectomy and partial hepatectomy with a 6 months evolution without complications and under a periodic surveillance protocol.

The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China.

BACKGROUND: Peri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of bile duct resection (BDR) remains controversial. METHODS: GBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses. RESULTS: A total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities. CONCLUSION: BDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.

Xanthogranulomatous Cholecystitis Mimicking Gall Bladder Cancer: a Diagnostic Dilemma and Review of Literature.

Xanthogranulomatous cholecystitis (XGC) is one of the rare variants of chronic cholecystitis which is characterized by inflammation of gall bladder along with infiltration by acute and chronic inflammatory cells. Intramural accumulation of lipid laden macrophages in GB wall is the hallmark of the disease. XGC results in dense adhesion of gall bladder (GB) to surrounding structures, like duodenum, colon, and stomach. The intense GB inflammation results in gall bladder perforation and development of fistulous communication between gall bladder and surrounding structures. This may also lead to formation of inflammatory mass which closely mimic gall bladder malignancy. Often differentiation from carcinoma of GB (Ca GB) on the basis of clinical presentation and even on intra-operative and radiological findings is difficult, and the issue could only be resolved on final Histopathology (HPE). We review presentation and investigation of a patient, discuss our approach in managing dilemma in treating such cases of XGC, and review the literature.

Misdiagnosis of carcinoma gall bladder in endemic regions.

BACKGROUND: Incidental carcinoma gall bladder and benign disease in radical cholecystectomy specimen is the cause of concern. We attempted to find out the incidence and reasons thereof in the present study. METHODS: Present study is a retrospective analysis of a prospectively maintained database between July 2002 and July 2019. All patients with a diagnosis of carcinoma gall bladder admitted for surgery were included. RESULTS: Out of 148 patients, 110 patients had carcinoma gall bladder (CAGB), while 38 patients (25.7%) had incidental carcinoma (under-diagnosis). Radical resection was done in 61/110 (55.4%) patients with clinical CAGB, where 15 (24.6%) patients had benign pathology ("over-diagnosis"). Overdiagnosis was due to xanthogranulomatous cholecystitis (n = 9), chronic cholecystitis (n = 2), tuberculosis (n = 2) and IgG4 related cholecystitis (n = 2). Among 61 patients, a history of weight loss and anorexia were significantly associated with malignancy. Asymmetrical wall thickness was significantly more common in benign mimickers. Among patients with incidental carcinoma, preoperative ultrasonography reported normal wall thickness of gall bladder in 28 (73.7%), thickened gall bladder wall in 6, and polyp in 3 patients. The resectability rate among incidental carcinoma was 27/38 (71.05%). CONCLUSION: Over-diagnosis of the carcinoma gall bladder was present in 24.6%. On the other hand, incidental carcinoma comprised 25.7% of all admissions for carcinoma gall bladder with resectability of 71%.

Feasibility and Safety of Laparoscopic Gallbladder Resection for Gallbladder Tumours.

BACKGROUND/AIM: The laparoscopic approach is not widely used for gallbladder tumours because of the high degree of malignancy associated with gallbladder cancer and technical difficulties. This study aimed to clarify the feasibility and safety of laparoscopic gallbladder resection for gallbladder tumours. PATIENTS AND METHODS: This retrospective study enrolled patients who underwent laparoscopic whole-layer cholecystectomy or laparoscopic gallbladder bed resection for gallbladder tumours between April 2010 and December 2020. We analysed the perioperative and oncological outcomes of patients with gallbladder carcinoma. RESULTS: The cohort comprised 31 patients, including 13 who underwent laparoscopic whole-layer cholecystectomy and 18 who underwent laparoscopic gallbladder bed resection. Twenty patients were diagnosed with gallbladder cancer. Three patients (15%) had metastases in harvested lymph nodes. No postoperative complications were observed. Recurrence occurred in four patients; the primary location was the liver in three patients and lymph node in two. The 1-, 3-, and 5-year recurrence-free survival and overall survival rates were 87%, 78.3%, and 58.8%, and 100%, 70.5%, and 70.5%, respectively. CONCLUSION: Our surgical strategy enables safe and curative gallbladder resection for gallbladder tumours, without excess or insufficient resection.

Surgical management of suspected gallbladder cancer: The role of intraoperative frozen section for diagnostic confirmation.

BACKGROUND: Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT). METHODS: MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes. RESULTS: A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p < 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically. CONCLUSIONS: The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

Comparative Study of Laparoscopic Versus Open Liver Resection in Gallbladder Cancer.

Background: In recent decades, laparoscopic liver resection (LLR) has been gradually adopted at high-volume centers, particularly for hepatocellular carcinoma and liver metastasis. However, LLR in patients with gallbladder cancer (GBC) is a controversial issue, and there are few studies of LLR for GBC. Our aim was to compare the outcomes of patients who underwent laparoscopic or open liver resection for GBC. Materials and Methods: All patients admitted with stage II or III GBC requiring liver resection, together with cholecystectomy and lymphadenectomy, were analyzed retrospectively. Patients with thickness of the resected liver specimen >2 cm in pathology reports were included. Results: A total of 56 patients with stage II or III GBC were included in this study; 23 (41.1%) underwent laparoscopic surgery and 33 (58.9%) underwent open surgery. Propensity score matching was performed using a 1:1 matching scheme. After matching, 12 patients were included in each group. The preoperative characteristics of both groups were similar, as were the operative times (laparoscopic versus open group: 237.5 minutes versus 272.5 minutes, respectively; P = .319) and blood loss (300 mL versus 275 mL, respectively; P = .307). The laparoscopic group had a significantly shorter postoperative hospital stay than the open surgery group (4.5 days versus 8 days, respectively; P = .012). There were no major complications in either group. There was no difference between the groups in the number of lymph nodes harvested at surgery (P = .910). There were no differences between the two groups in disease-free (P = .503) or overall (P = .719) survival. Conclusion: LLR extended to GBC provides outcomes similar to those of open surgery. With increasing experience, LLR can be a viable alternative to open surgery for GBC.

Gallbladder cancer: Historical treatment and new management options.

Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.

Bi-segmentectomy versus wedge hepatic resection in extended cholecystectomy for T2 and T3 gallbladder cancer: A matched case-control study.

BACKGROUNDS/AIMS: Extended cholecystectomy (EC) is the mainstay of treatment in most patients with potentially curable gallbladder cancer (GBC). The optimum extent of hepatic resection in EC is debatable. METHODS: This retrospective study was conducted on patients with GBC who received EC from May 2009 to February 2019. Based on the extent of hepatic resection, patients were divided into ECB (EC involving bi-segmentectomy s4b&5) and ECW (EC involving wedge hepatic resection) groups. Patients with T1 GBC, T4 GBC, and benign diseases were excluded. Post-exclusion, both groups were matched for T and N stage. Matched groups were then compared. RESULTS: Out of a total of 161 patients who received EC, 86 patients had ECB and 75 patients had ECW. After exclusion and matching, both ECB and ECW groups had 35 patients. Their demographic and clinical profiles were comparable. Surgical blood loss (p = 0.005) and postoperative complication rate (p = 0.035) were significantly less in the ECB group. For ECB vs. ECW, mean recurrence-free survival (RFS) was 58.2 months vs. 42.3 months (p = 0.264) and overall survival (OS) was 61.5 months vs. 43.4 months (p = 0.161). On univariate analysis, higher T and N stages were associated with poor prognosis. On multivariate analysis, higher T stage, N stage, and American Society of Anaesthesiologists grade were associated with poor RFS and OS. CONCLUSIONS: The survival after ECB for T2 and T3 GBC was not significantly superior to that after ECW. However, surgical blood loss and postoperative complications were lower following ECB.

Primary Small Cell Neuroendocrine Tumour of Gallbladder Presenting as Pyrexia of Unknown Origin.

Herein, we report a case of primary small cell neuroendocrine tumor (NET) of the gallbladder in a 45-year-old female who presented with complaints of fever accompanied by abdominal pain on the right upper quadrant for one month. Contrast-enhanced computed tomography abdomen showed a large gallbladder mass. It was infiltrating the segments IVa, IVb, and V of the liver. Ultrasound-guided fine-needle-aspiration-cytology was performed. Based on preoperative pathological and immunohistochemical investigations, it was diagnosed to be a primary small cell NET of the gallbladder. The patient underwent radical cholecystectomy after three cycles of cisplatin-based neoadjuvant chemotherapy. She had an uneventful recovery and received adjuvant chemo-radiotherapy. The patient was well at the 18-month follow-up.

Laparoscopic versus open extended cholecystectomy with bi-segmentectomy (s4b and s5) in patients with gallbladder cancer.

INTRODUCTION: The outcome of laparoscopic extended cholecystectomy (EC) with wedge hepatic resection (LECW) in patients with gallbladder cancer (GBC) has been compared with that of open EC with wedge hepatic resection (OECW), but studies comparing laparoscopic EC with bi-segmentectomy (LECB) with open EC with bi-segmentectomy (OECB) are lacking. PATIENTS AND METHODS: This retrospective study comprised of 68 patients with GBC who were offered either LECB or OECB from July 2011 to July 2018. Patients were divided into laparoscopic group (LG) and open group (OG), and appropriate statistical methods were used for comparison. RESULTS: Out of the total 68 patients, 30 patients were in LG and 38 patients were in OG. Demographic, clinical and biochemical characteristics were similar except significantly higher number of male patients in OG (P = 0.01). In LG versus OG, the mean operation time was 286 versus 274 min (P = 0.565), mean blood loss was 158 versus 219 ml (P = 0.006) and mean hospital stay was 6.4 versus 9 days (P = 0.0001). The complication rate was 16.6% in LG and 31.5% in OG, but this difference was not statistically significant (P = 0.259). The median number of lymph nodes was 12 in both LG and OG (P = 0.62). Distribution of patients among American Joint Committee on Cancer stages I to IV was similar in both the groups (P = 0.5). Fifty percent of the patients in both the groups received adjuvant treatment (P = 1). In LG versus OG, the recurrence rate was 20% versus 28.9% (P = 0.4), mean recurrence-free survival was 48 months versus 44 months (P = 0.35) and overall survival was 51 months versus 46 months (P = 0.45). In LG versus OG, 1, 3 and 5-year survival was 96% versus 94%, 79% versus 72% and 79% versus 62% (P = 0.45). The median follow-up was statistically significantly shorter (24 vs. 36 months) in LG versus OG (P = 0.0001). CONCLUSIONS: The oncological outcome and survival after LECB in patients with resectable GBC is not inferior to that after OECB. Laparoscopic approach has a potential to improve perioperative outcome in patients with GBC.

Hotspots and disputes concerning surgical management of gallbladder cancer / 西安交通大学学报(医学版)

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary tract, with a high degree of malignancy and poor prognosis. R0 resection is the basic principle of surgical treatment of GBC. However, disputes still exist over the extent of liver resection, extrahepatic bile duct resection, range of lymphadenectomy, surgical treatment of GBC diagnosed during or after surgery, and the application of laparoscopy in GBC. This paper reviews the progress in surgical treatment of GBC and discusses the disputes over surgical treatment in order to provide reference for clinical research and treatment of GBC in clinical work.