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Radiomics is a method that extracts many features from medical images using various algorithms. Medical nomograms are graphical representations of statistical predictive models that produce a likelihood of a clinical event for a specific individual based on biological and clinical data. The radiomic nomogram was first introduced in 2016 to study the integration of specific radiomic characteristics with clinically significant risk factors for patients with colorectal cancer lymph node metastases. Thereby it gained momentum and made its way into different domains of breast, liver, and head and neck cancer. Deep learning-based radiomics which automatically generates and extracts significant features from the input data using various neural network architectures, along with the generation and usage of nomograms are the latest developments in the application of radiomics for the diagnosis of gall bladder carcinoma. Although radiomics has demonstrated encouraging outcomes in the diagnosis of gall bladder carcinoma, but most of the studies conducted suffer from a lack of external validation cohorts, smaller sample sizes, and paucity of prospective utility in routine clinical settings. [ABSTRACT FROM AUTHOR] more...

The author outlines his philosophy and practice of management of gall bladder cancer based on his more than three-decade experience at a large tertiary level super-specialty referral hospital attached to a university-status teaching institution at Lucknow in northern India where GBC is very common. [ABSTRACT FROM AUTHOR] more...

Background: Robotic surgery has demonstrated outcomes comparable or superior to open and laparoscopic surgeries for extended cholecystectomy.1, 2, 3, 4, 5, 6, 7–8 Despite its advantages, the minimally invasive robotic single-port (SP) system remains underutilized in complex hepatobiliary pancreatic surgery due to instrument limitations and retraction issues.9,10 This study evaluated the feasibility, safety, and effectiveness of the da Vinci SP system in gallbladder cancer surgery. The study was approved by the Ethics Committee of OOO University Hospital (IRB no. DAUH IRB-24-081) and conducted in accordance with the principles of the Declaration of Helsinki. The requirement for informed consent was waived due to the study's retrospective design. Methods: A 62-year-old woman with a diagnosis of gallbladder cancer was referred for surgery. Preoperative computed tomography (CT) scans showed no evidence of metastasis (T2N0). Therefore, a robotic SP extended cholecystectomy was planned. Figure 1 shows a 30-mm SP port and a 1-mm assistant port inserted for the procedure. Due to the absence of an energy device for the liver wedge resection, Maryland bipolar forceps were used, mimicking the Kelly clamp crushing technique. A monopolar cautery hook was used for lymph node resection of stations 7, 8, 12, and 13 (Fig. 2). Results: The total duration of the operation was 226 min, with an estimated blood loss of 200 ml. The CT scan on day 5 showed no abnormalities, and the patient was discharged routinely on day 7 (Fig. 3). The pathologic examination confirmed adenocarcinoma (T2a) with clear resection, and all six lymph nodes tested negative for malignancy. Conclusions: This study underscores the adequacy of robotic surgeries and emphasizes the potential of the da Vinci SP system in hepatobiliary surgery. Despite current challenges related to instrument limitations, the authors are confident that the SP system will evolve into a crucial asset for hepatobiliary surgical practices in the foreseeable future. [ABSTRACT FROM AUTHOR] more...

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. [ABSTRACT FROM AUTHOR] more...

Purpose: The data on the prognostic significance of red cell distribution width (RDW) in gallbladder cancers is sparse, especially in the potentially resectable cohort of patients. The aim was to assess the prognostic significance of RDW in gallbladder cancer patients undergoing surgery. Methods: Retrospective analysis of prospectively maintained database of gallbladder cancer patients undergoing surgery at a tertiary cancer institute from 2010 till 2018. Baseline values were collected. Patients were grouped as per the median RDW value and compared. Survival analysis was done using the Kaplan Meier method. Results: A total of 605 patients were included. The median follow up period was 23 months (range: 6–120 months). The median value of RDW was 14. Comparison between RDW > 14 and RDW < 14 groups showed no difference in outcomes. RDW did not predict overall survival or recurrences. However, in combined stages II and III, a statistically significant improvement in OS and DFS (p < 0.001) was noted in the RDW < 14 group. Conclusion: RDW did not predict recurrence or survival in potentially resectable gallbladder cancer patients. However, in the subset of stages II and III in combination, lower RDW value was associated with better outcomes. More prospective studies are needed to conclusively establish the prognostic value of RDW. [ABSTRACT FROM AUTHOR] more...

Background: Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. Methods: Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. Results: The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. Conclusion: Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals' expectations. [ABSTRACT FROM AUTHOR] more...

Aim of doing this review was to give a uniform consensus on prognostic impact of tumor location (hepatic vs peritoneal), liver resection and adjuvant chemotherapy in gall bladder cancer and, to compare them with previous well-studied factors of survival. We systematically review PubMed, Scopus and Cochrane for relevant articles with no date restrictions, language was restricted to English. Those articles were included that had provided Hazard ratio (HR) of survival for T2 gall bladder cancer. We identified nine retrospective studies published between 2014 and 2020 with 2345 patients. Meta-analysis showed that T2b (hepatic) cancers had higher odds of mortality (HR 3.16 [2.11, 4.74], I2 = 0%). Liver resection was associated with significantly higher odds of 5-year overall survival only in T2b (2.20 [1.33, 3.63], I2 = 67%), adjuvant chemotherapy was not associated with any significant decrease in mortality risk (0.98 [0.83–1.16]. I2 = 20%). Hepatic sided gall bladder tumors carry higher odds for mortality and recurrence. T2a tumors can be managed without hepatic resection. To risk stratify patients we also formulated a scoring system for mortality risk. [ABSTRACT FROM AUTHOR] more...

Gall bladder cancer (GBC) is an aggressive and most common malignancy of biliary tract lacking effective treatment due to unavailability of suitable biomarkers and therapeutics. SMAD4 is an essential mediator of transforming growth factor-β pathway involved in various cellular processes like growth, differentiation and apoptosis and also recognized as therapeutic target for GBC and other gastrointestinal tract cancers. In the present study, 3D structure of SMAD4 mutants was optimized through molecular dynamics simulation (MDS) along with wildtype. Furthermore, binding site of protein was predicted through hybrid approach and structural based virtual screening against two drug libraries was performed followed by docking. MDS of top docking score protein–ligand complexes were carried, and binding free energy was rescored. Two potential inhibitors, namely ZINC2098840 and ZINC8789167, were screened that displayed higher binding affinity towards mutant proteins compared with wildtype and both hydrophilic as well as hydrophobic interactions play a crucial role during protein–ligand binding. Current study identified novel and potent inhibitors of SMAD4 mutant that could be used as a drug candidate for the development of personalized medicine for gall bladder and other associated cancers. [ABSTRACT FROM AUTHOR] more...

Opinion Statement: The standard of care first-line therapy for patients with advanced biliary tract cancers eligible for treatment continues to be the combination of gemcitabine and cisplatin. Based on the promising results of a phase II study, an ongoing multi-institutional phase III study is assessing the benefit of adding nab-paclitaxel to the chemotherapy doublet, and appropriate patients should be considered for enrollment at participating centers. We would recommend early comprehensive genomic profiling of patients' tumors to identify potentially targetable aberrations with available therapies. Results with therapeutic implications include tumors with microsatellite instability/deficient mismatch repair, alterations in FGFR, IDH1/2, and HER-2, and potentially other molecular vulnerabilities. Patients in whom a targetable genomic abnormality is found should be matched with appropriate agent. If a targetable fusion or mutation is not detected, patients eligible for second-line therapy should be considered for either clinical trial enrollment or a second-line cytotoxic chemotherapy regimen such as modified FOLFOX. Strategies incorporating immunotherapy into the treatment of patients with microsatellite stable advanced biliary tract cancers have yielded largely disappointing results thus far, and routine use of checkpoint inhibitors outside of a clinical trial is not recommended. [ABSTRACT FROM AUTHOR] more...

Manual for staging of cancer published by the American Joint Committee on Cancer (AJCC) is the most widely used for cancer staging throughout the world. AJCC has published the 8th edition of the manual in 2016, which is currently the latest edition. This review article is a comparison of important changes in TNM and prognostic staging of surgical cancers in the latest edition compared to the previous one, i.e., 7th edition that was published in 2009. [ABSTRACT FROM AUTHOR] more...

Gall bladder carcinoma (GBC) is most prevalent in the northern and northeastern states of India. The term ‘Incidental gall bladder carcinoma’ (IGBC) refers to the diagnosis coming as a surprise finding upon histopathological examination of the cholecystectomy specimen and its incidence varies from 0.35-2%. The conventional practice of submitting all excised gall bladder specimens for histopathological examination has also been challenged by some authors who feel that a selective approach should be adopted, in order to save costs and time. Our experience in this respect, from a tertiary level teaching hospital in southwestern India, is presented here along with a review of literature. Data in respect of all patients who underwent cholecystectomy for benign disorders from 01 Dec 2012 to 30 Nov 2014 was collected prospectively. In addition, retrospective collation of data from hospital records for the previous 2 years was undertaken. Gall bladder wall thickness ≥ 4 mm, on USG examination, was taken as abnormal. All excised gall bladder specimens were opened and examined immediately after surgery in the operation theatre and then submitted for histopathological examination. Statistical analysis was performed using SPSS 19.0. A p value of less than 0.05 was considered significant. A total of 1123 patients underwent cholecystectomy for benign gallbladder pathologies. IGBC was detected in seven (three male and four female) patients. Only one, out of these seven patients, had focal gallbladder wall thickening at the fundus while the other six cases did not have any macroscopic abnormality of the gallbladder wall or mucosa. The mean age of the patients with IGBC was 63.86 years and it was significantly higher as compared to those with benign histology (p value = 0.001). Furthermore, an age of more than 50 years was found to be significantly associated with IGBC (X2 = 9.446, p value = 0.002). In this series, IGBC was present in 0.62% of patients undergoing cholecystectomy for benign gall bladder pathologies. A patient’s age of more than 50 years was significantly associated with IGBC and we did not find any correlation between the symptomatology, ultrasound findings and macroscopic appearance of the specimen and the presence of IGBC. Hence, we feel that the practice of routine submission of all excised gall bladders for HPE should continue. [ABSTRACT FROM AUTHOR] more...

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients’ survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC. [ABSTRACT FROM AUTHOR] more...

Introduction: Gall bladder cancer (GBC) has high prevalence in the Indo-Gangetic belt in India. While the first-line chemotherapy (CT1) has been established as gemcitabine-platinum doublet in advanced GBC, there is no standard recommendation or guidelines regarding feasibility of second-line therapy. Methods: We performed a retrospective analysis of all patients who received second-line of chemotherapy (CT2) at our institution from July 2012 to December 2014. Patient records were examined for efficacy and toxicity of administered CT2, along with response rates (RR) and survival. Potential prognostic factors were also evaluated. Results: Eighty-seven patients received CT2 in the predefined period. Ninety-nine percent of patients had received a gemcitabine-based regimen as CT1 with a median progression-free survival (PFS) of 5 months before CT2. 51.7 % patients had undergone surgery prior with 5.7 % patients having received radiotherapy previously. Prior to beginning CT2, PS was 0/1 in 67.8 % patients, albumin was >4 g% in 40.2 % and CA 19.9 was raised in a majority (66.7 %) patients, respectively. As per institution protocol, a majority of patients (89.6 %) were administered CAP-IRI regimen. Overall RR and disease control rates (DCR) were 21.8 % and 41.3 %, respectively. Median progression-free survival (PFS) and overall survival (OS) were 6 and 8 months, with no significant differences between CAP-IRI and other regimens. Adverse effects were tolerable, with dose reduced upfront in 23 % patients and 11.5 % patients during subsequent cycles of CT. ECOG Performance Status (PS) of 0/1 was a significant prognostic variable for OS on multivariate analysis ( p = 0.003). Conclusion: CAP-IRI is a well-tolerated second-line chemotherapeutic regimen in patients with advanced GBC. Careful selection of patients is required when administering second-line chemotherapy to advanced GBC patients, with particular emphasis on ECOG PS. [ABSTRACT FROM AUTHOR] more...

Purpose: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has increased the rate of liver resections in patients with marginal future liver remnant. We here describe a modified ALPPS procedure with splitting-off the central liver segments for staged mesohepatectomy in patients with advanced gall bladder cancer. Methods: A double in situ split for ALPPS (DALPPS) is performed with splitting-off the central liver segments (segments 1, 4, 5, and 8). This induces a rapid hypertrophy of the left lateral (segments 2/3) and right posterior sectors (segments 6/7). An intrahepatic right posterior approach during splitting-off the right posterior sector is introduced as a part of this new procedure. This approach facilitates the dissection and ligation of the right anterior branch of the portal vein (segments 5 and 8) while the liver hilum remains untouched during the first step of surgery. Results: Two patients with advanced gall bladder cancer were treated with the DALPPS procedure till date. After a short interval (7-9 days), a rapid hypertrophy of the left lateral and right posterior sector was observed (hypertrophy up to 72.6 and 54.6 %, respectively). A staged mesohepatectomy including caudate lobectomy and resection of the extrahepatic bile duct was then performed safely. There was no surgical-technical morbidity. No signs of posthepatectomy liver failure according to the 50-50 criteria were seen. However, one patient died from severe ARDS attributed to the preoperative chemotherapy. Nevertheless, this complication is deemed to be surgery related. Conclusions: The DALPPS procedure is a new surgical technique for staged mesohepatectomy for patients with small future liver remnant in size or in function. However, appropriate patient selection is mandatory to avoid morbidity and mortality. [ABSTRACT FROM AUTHOR] more...

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease. [ABSTRACT FROM AUTHOR] more...

One of the criteria for recommending cholecystectomy for silent gall stones, is gall stones in regions with high incidence of gall bladder cancer. Both gall stones and gall bladder cancer are common in North India. All tertiary care centres in India report high rates of gall bladder cancer (GBC) incidence and poor treatment outcomes in the majority of cases due to advanced stage of presentation. Csendes of Chile has reported very high incidence of gallbladder cancer in Chile and Bolivia and advocated prophylactic cholecystectomy in asymptomatic patients. Incidence rate of gall bladder cancer in Indian males is equal to that of Chile, whereas in females, the rates are almost double the rates of Chile. Indians have also been found to have high concentrations of heavy metals in gall bladder wall, and antibodies to tumor suppressor genes. In India, gall bladder cancer is the commonest GI cancer in women and fourth commonest cancer overall in the female population. In view of the epidemiology and clinical scenario of gall bladder cancer and proven safety of laparoscopic cholecystectomy, there is a need to act before it is too late in the current rates of gall bladder cancer. This study looks at the evidence correlating gall stones and gall bladder cancer, in relation to India. There is pressing evidence today to justify a strategy of prophylactic cholecystectomy in silent gall stones in North India. Data for this study was selected through an internet based search for literature concerning gall stones and gall bladder cancer in India, and for prophylactic cholecystectomy. [ABSTRACT FROM AUTHOR] more...

Purpose: The purpose of the study was to analyse outcomes with adjuvant concurrent chemoradiotherapy (cCRT) followed by adjuvant chemotherapy (AC) in radically resected gall bladder carcinoma (GBC) in Indian patients. Methods and Materials: We retrospectively reviewed the records of GBC patients who received adjuvant cCRT after extended cholecystectomy (EC) between January 2007 and December 2011. Patterns of recurrence, disease-free survival (DFS), overall survival (OS) and adverse prognostic factors were evaluated. Results: Thirty-two patients were analysed. At a median follow-up of 53 months, 40 % of patients had recurrence either locoregionally (12 %) or had distant metastases (28 %). The 5-year OS and DFS was 25 % and 53 %, respectively. When prognostic factors were evaluated, the median OS was 51 versus 23 months for node-negative ( n = 8) versus node-positive disease ( n = 24), not reached versus 34 months for stage 2 ( n = 4) versus for stage 3 ( n = 28), 46 versus 23 months for R0 ( n = 11) versus R1 resection ( n = 21), 51 versus 12 months ( p = 0.15) for well-differentiated ( n = 16) versus poorly differentiated tumours ( n = 8), and 10 versus 51 months for lymphovascular invasion presence ( n = 4) versus absence ( n = 28) ( p = 0.01). Conclusion: Outcome in Indian patients with cCRT followed by AC is similar to that reported in the literature. Adjuvant cCRT followed by AC improves outcomes in patients with R1 and node-positive disease. Advanced stage, nodal positivity, poor differentiation, presence of perineural invasion and lymphovascular invasion are adverse prognostic features. Further research is required with treatment intensification in patients with adverse prognostic factors to improve outcome. [ABSTRACT FROM AUTHOR] more...

Gall bladder carcinoma (GBC) is the seventh most common cancer across the globe and the most common malignancy of the biliary tract. Most GBC related deaths occur due to secondary progression and metastasis to distant organs. Epithelial-mesenchymal transition (EMT) is an important pre-requisite for tumor metastasis, however its mechanism in GBC has not yet been defined. Using the GBC-SD cell line, we have uncovered an important mediator, poly r(C) binding protein-1 (PCBP1), of transforming growth factor-beta (TGF-β)-induced EMT in GBC. Our results show that TGF-β treatment resulted in PCBP1 phosphorylation in accordance with similar observation in other model systems. We further showed through gain- and loss-of-function assays that PCBP1 expression levels regulate the capacity of GBC-SD cells to migrate and invade in vitro. Finally, our results showed that PCBP1 expression levels also regulate generation of CD44CD24 progenitor cell population in GBC-SD cells after TGF-β treatment. Cumulatively, our results indicate, pending further validation, that PCBP1 might be a prognostic marker for GBC metastasis. [ABSTRACT FROM AUTHOR] more...

Gall bladder cancer is a common cancer in the Ganges belt of North-eastern India. In view of incidental diagnosis of gall bladder cancer by physicians and surgeons, the treatment is not optimised. Most patients present in advanced stages and surgery remains the only option to cure. This review highlights the current evidence in advances in systemic therapy of gall bladder cancer. [ABSTRACT FROM AUTHOR] more...

Gallbladder cancer (GBC) is a lethal and a common malignancy affecting mostly females. There are restricted high incidence pockets across the world and in northern India highest incidence of GBC is reported from the Gangetic belt. The etiology of this disease remains largely unknown though several risk factors have been stated. The genetic aberrations in GBC involving mutations in tumor suppressor genes and oncogenes have been reported in literature. However, there is scarcity of data regarding epigenetic changes that may also be involved in gallbladder carcinogenesis. This review attempts to summarize our current understanding of the epigenetic changes in GBC. [ABSTRACT FROM AUTHOR] more...

Purpose: Gallbladder and pancreas share common embryological origin, and malignancies of these organs may share common tumor antigens. CA 242 is a tumor marker for pancreatic cancer, but has not been studied in gallbladder cancer (GBC). We measured serum CA 242 levels in patients with GBC and compared it with those in patients with gallstones (GS) and healthy volunteers. Methods: We enrolled consecutive patients with GBC (cases), GS (disease controls), and healthy volunteers (healthy controls). Serum CA 242, CEA, and CA 19-9 levels were measured using ELISA. Receiver operator curve was plotted for all the three markers. Results: We studied 117 patients with GBC, 58 with GS, and 10 healthy volunteers. Among patients with GBC, 81 (69%) also had GB calculi. Patients with GBC more often had elevated CA 242 levels (64%) compared to those with GS (17%; p < 0.001) and healthy controls (0%; p < 0.001). The median levels of CA 242 was higher in the GBC group (59 [199] U/ml) compared to the GS group (10 [13] U/ml; p < 0.001) and the control group (3 [14.5] U/ml; p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive values of CA 242 for diagnosis of GBC were 64%, 83%, 88%, and 53%, respectively. At a cutoff of 45 U/ml, the specificity and PPV increased to 100%. CA 242 had higher AOC (0.759) compared to CEA (0.528) and CA 19-9 (0.430). Conclusions: CA 242 is a promising tumor marker for GBC and performs better than CEA and CA 19-9. [ABSTRACT FROM AUTHOR] more...

Abstract: Introduction: Adenomyomatosis, or diverticular disease of the gallbladder, is an acquired hyperplastic lesion characterized by excessive proliferation of the surface epithelium with deepened invaginations extending into the thickened muscular layer of the gallbladder wall. The radiologic evidence of both adenomyomatosis and gallbladder cancer is focal or diffuse thickening of the gallbladder wall . Focal or diffuse gallbladder wall thickening is a relatively frequent observation on CT and is often incidental. It can be a dilemma for interpreting radiologists . Aim of the work: The purpose of this study is to determine the role of MDCT in differentiating adenomyomatosis from gallbladder cancer. Patients: The study included 20 patients already pathologically diagnosed as adenomyomatosis or gall bladder cancer, and who had undergone pre-operative CT. Methods: Preoperative CT is reviewed for the presence and nature of morphologic gallbladder abnormalities, including the presence of intramural diverticula (Pearl necklace sign) and the presence of a non-interrupted mucosal enhancement line. Results: Pearl necklace sign was 80% accurate for the diagnosis of adenomyomatosis. Mucosal enhancement line was 100% accurate for the same diagnosis. Conclusion: MDCT is an accurate technique for differentiating between gall bladder adenomayomatosis and cancer. [Copyright &y& Elsevier] more...

Purpose: Treatment of unresectable locally advanced gallbladder cancers (LAGBC) usually consists of various palliative strategies which provide only a modest survival benefit. Here, we present a series of three patients of LAGBC-treated consecutively at our center with preoperative chemoradiation using tomotherapy and concurrent gemcitabine. Methods: All three cases were reported to be adenocarcinoma by biopsy or fine-needle aspiration cytology. All the patients underwent positron emission tomography with computerized tomography scan to rule out distant metastasis and also to map the extent of disease for radiotherapy planning. Preoperative chemoradiation consisted of gemcitabine at 300 mg/m weekly and tomotherapy with daily image guidance with MVCT over 5 weeks to a dose of 57 Gy in 25 fractions to the gross tumor and 45 Gy in 25 fractions to the clinical target volume to cover the areas of microscopic spread. Results: Complete metabolic and radiologic response was observed for 2 patients and partial response for 1 patient. Two patients underwent complete surgical excision of which 1 patient had complete pathological response and 1 patient had small residual tumor at the primary and no nodal metastasis. The third patient could not undergo surgery due to medical reasons. Conclusions: The clinical outcome for unresectable LAGBC with preoperative chemoradiation in terms of feasibility, safety, and survival is encouraging. This treatment strategy has a curative potential for the otherwise fatal disease. [ABSTRACT FROM AUTHOR] more...

Background: Quality of life measurement in cholangiocarcinoma and gallbladder cancer involves the assessment of patient-reported issues related to the symptoms, disease and treatment of these tumours. This study describes the development of the disease-specific quality of life (QoL) questionnaire for patients with cholangiocarcinoma and gallbladder cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30 core cancer questionnaire.Methods: Phases 1-3 of the guidelines for module development published by the EORTC were followed, with adaptations for incorporation of questions from existing modules.Results: A total of 47 QoL issues (questions) were identified; 44 questions from the two related validated questionnaires, the EORTC QLQ-PAN26 (pancreatic module) and the EORTC QLQ-LMC21 (liver metastases module), two from the Functional Assessment of Cancer Therapy hepatobiliary module questionnaire in the literature search and one from healthcare professional interviews. Following phase 1 and 2 interviews with patients (n=101) and health care professionals (n=6), a 23-question provisional questionnaire was formulated. There were five questions from PAN26, 15 from LMC21 and three extra questions. In phase 3, the provisional item list was pre-tested in 52 patients in four languages and this resulted in a 21-item module.Conclusion: This is the only disease-specific QoL questionnaire for patients with cholangiocarcinoma and gallbladder cancer, and initial assessments show it to be accurate and acceptable to patients in reflecting QoL in these diseases. [ABSTRACT FROM AUTHOR] more...

There is a need for effective chemotherapy protocols for gall bladder cancer (GBC). Gemcitabine has antitumor activity in pancreatic cancer. Oxaliplatin is effective in GI cancers. Based on evidence of synergy between these two, we designed this study to evaluate efficacy of this combination in unresectable GBC. Unresectable GBC was enrolled for single center phase II study. Drugs gemcitabine 900 mg/m2 and oxaliplatin 80 mg/m2 IV infusion (Oxigem) on days 1 and 8 every 3 weeks for a maximum of six cycles or unacceptable toxicity which ever was earlier. Fifty patients were enrolled and analysis was restricted to 48 who were treated. Median age was 50 years and 31 patients were females. CR 3 (6.2%), PR 7 (15%), SD 17 (35.4%), and PD 18. One had complete pathological response. Median OS and PFS were 7.5 and 3 months, respectively. OS in responders was 10.5 versus 4 months in non-responders ( p < 0.0000). Eleven patients (23%) survived for a year or more. There was no toxic death and grade III/IV toxicity seen in 10 (22%) patients: diarrhea 3, vomiting 2, neutropenia and thrombocytopenia 5 patients. This combination of Oxigem effective in unresectable GBC. It may even induce complete pathological response. One-year survival was 20%. There is a need for controlled trial to assess efficacy of this combination. [ABSTRACT FROM AUTHOR] more...

The presence of biliary obstruction in patients with gallbladder cancer (GBC) is generally viewed as an indicator of advanced disease, inoperability and poor prognosis. Data was collected from patients with GBC with obstructive jaundice who underwent resection during the period January 2001 to October 2003. Systematic analysis of prospective data was undertaken; patients were analyzed for resectability, post-operative morbidity, mortality and disease-free survival. During this period 14 patients with GBC with biliary obstruction underwent resection with curative intent. In these jaundiced patients, the resectability rate was 27.45% (14 of 51). In the jaundiced group the mortality was 7.14% the morbidity rate 50%, the mean disease free survival was 23.46 months (median 26 months and range of 2 to 62 months). Seven patients (50%) survived more than two years. Biliary obstruction in gall bladder cancer is not sine qua non of inoperability and resection results in meaningful prolongation of survival. [ABSTRACT FROM AUTHOR] more...

Biliary tract cancer is one of the most aggressive and chemotherapy-refractory tumors. Although only curative treatment modality is surgery, most patients are not suitable for surgery due to advanced stage of the disease at diagnosis. Thus most patients with biliary tract cancer are possible candidates for palliative chemotherapy. The standard chemotherapeutic regimen is still to be defined, however. We performed a phase II study of combination chemotherapy with capecitabine and cisplatin in these patients to evaluate efficacy and toxicity of the regimen. Patients with previously untreated metastatic, recurrent, or inoperable biliary tract cancer were enrolled. Eligible patients were screened as following: (1) histologically confirmed, (2) age between 18 and 75 years, (3) at least one measurable lesion according to RECIST criteria, (4) ECOG performance status ≤2, (5) a life expectancy of at least 3 months, and (6) adequate laboratory values. Patients received capecitabine (2,500 mg/m2/day, days 1 to 14) and cisplatin (60 mg/m2, day 1) every 3 weeks. Response was assessed for every two cycles of chemotherapy and treatment was stopped when tumor had progressed or stable with no further response. Thirty-two patients were enrolled, 20 (62.5%) were male and 12 (37.5%) were female and the median age was 54 years (33–71 years). Fifteen patients (46.9%) had gallbladder cancer, 13 (40.6%) had intrahepatic cholangiocarcinoma, and 4 (12.5%) had extrahepatic biliary cancer. The most frequent metastatic sites were lymph nodes (20/32, 62.5%) and liver (28/32, 56.3%). No complete response was observed and partial response was observed in 13/32 patients. By the intent-to-treat analysis, the overall response rate was 40.6% (95% CI, 23.7–59.4) with 0 CR and 13 PRs. Stable disease was observed in 3 patients (9.4%), and 11 patients (34.4%) had progressive disease. The median time to progression was 3.5 months (95% CI, 1.3–5.8), and the median overall survival was 12.4 months (95% CI, 6.3–18.5) after the median follow-up duration of 9.5 months (4.8–26.1 months). A total of 108 cycles of chemotherapy was delivered. Grade 3 hematologic toxicities included neutropenia (5, 15.6%), anemia (1, 3.1%), and thrombocytopenia (1, 3.1%) per patient, and no grade 4 hematologic toxicities were observed. Grade 3 non-hematologic toxicities included hyperbilirubinemia (2, 6.3%), increase of alkaline phosphatase (2, 6.3%), hand–foot syndrome (2, 6.3%), anorexia, and diarrhea (1, 3.1%) per patient, respectively. There was no treatment-related death. The combination chemotherapy of capecitabine and cisplatin demonstrated a promising antitumor activity with mild toxicity profile in patients with advanced biliary tract cancer. [ABSTRACT FROM AUTHOR] more...

The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination in unresectable gall bladder cancer patients. The secondary objectives were to evaluate the toxicity, time to progressive disease, and overall survival. Chemonaïve patients with histologically proven, unresectable bidimensionally measurable gall bladder cancer were enrolled into this study. All patients were required to have a Zubrod's performance status ?2, no prior radiotherapy, and adequate major organ function. Patients received gemcitabine (1000?mg?m-2 intravenously over 30-60?min) on days 1 and 8, and cisplatin (70?mg?m-2 intravenously over 2?h) on day 1, every 21 days. Response assessment was done by a CT scan after every other cycle of chemotherapy. In all, 30 patients were eligible for efficacy and toxicity analysis. There were four (13.3%) complete responders, seven (23.3%) partial responders, and seven (23.3%) with stable disease, with four (13.2%) patients showing disease progression. The median time to progression was 18 weeks (95% confidence interval (CI) 14-24 weeks), and the median duration of response was 13.5 weeks (range 5.5-104 weeks). The median overall survival was 20 weeks (95% CI 14-31 weeks), with 1-year survival rate of 18.6%. WHO grade 3 or 4 anaemia was seen in seven (23.3%) and four (13.3%) patients, respectively. Five (16.6%) patients each experienced grade 3 or 4 neutropenia, and grade 3 or 4 thrombocytopenia was seen in three (10%) and two (6.6%) patients, respectively. The present study shows that gemcitabine/cisplatin combination is well tolerated and active in advanced unresectable gall bladder cancer.British Journal of Cancer (2004) 90, 1516-1520. doi:10.1038/sj.bjc.6601736 www.bjcancer.com Published online 16 March 2004 [ABSTRACT FROM AUTHOR] more...

Human mast cells are categorized into mast cells positive only for tryptase (MCT) and mast cells positive for both tryptase and chymase (MCTC). The structural appearance of tryptase-, and chymase-positive mast cells in metastatic liver disease and the variations in MCT and MCTC numbers in accordance with the origin of the primary tumors have been described in the present study. Liver mast cells are analyzed immunocytochemically using tryptase and chymase and by quantitative morphometry in 30 patients with colorectal ( n=15), gastric ( n=8), and pancreatic ( n=7) cancers and in 5 control livers. The numbers of MCT and MCTC are increased in the extratumoral liver tissue (mainly portal tracts) as compared to controls. The numbers of MCT and MCTC in and around metastases with moderate or high grade of differentiation are statistically significantly higher, as compared to those with low grades of differentiation. The numbers of MCTC are greater than that of MCT in the extratumoral liver tissue and in metastases themselves. Ultrastructurally, mast cells immunostained with tryptase and chymase have three types of granules: electron dense granules with darkly precipitated reaction product, electron lucent granules without reaction product and electron lucent granules with sparse reaction product (altered granules). Both types of mast cells have small and large in size granules, resembling the MCTC phenotype described earlier. Tryptase-positive mast cells have granules with discrete scrolls and particulate and beaded pattern. Chymase-positive mast cells have granules with finely granular or particulate material. Substance P (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed in livers with metastases. The present study suggests that liver mast cells are mainly from the MCTC type, and are accumulated in peritumoral and metastatic areas. They may play a role in the formation of tumor stroma, or in tumor immunology in liver metastases from various primary gastrointestinal cancers. [ABSTRACT FROM AUTHOR] more...

In a case-control study using a large UK primary care database, we found that non-steroidal anti-inflammatory drugs had no protective effect against biliary carcinomas (cholangiocarcinoma and gall bladder cancer). Increased risks were observed for cigarette smoking, diabetes, gallstone disease and obesity. [ABSTRACT FROM AUTHOR] more...