Efficient chimeric antigen receptor targeting of a central epitope of CD22.

Chimeric antigen receptor (CAR) T-cell therapy has had considerable success in the treatment of B-cell malignancies. Targeting the B-lineage marker CD19 has brought great advances to the treatment of acute lymphoblastic leukemia and B-cell lymphomas. However, relapse remains an issue in many cases. Such relapse can result from downregulation or loss of CD19 from the malignant cell population or expression of alternate isoforms. Consequently, there remains a need to target alternative B-cell antigens and diversify the spectrum of epitopes targeted within the same antigen. CD22 has been identified as a substitute target in cases of CD19-negative relapse. One anti-CD22 antibody-clone m971-targets a membrane-proximal epitope of CD22 and has been widely validated and used in the clinic. Here, we have compared m971-CAR with a novel CAR derived from IS7, an antibody that targets a central epitope on CD22. The IS7-CAR has superior avidity and is active and specific against CD22-positive targets, including B-acute lymphoblastic leukemia patient-derived xenograft samples. Side-by-side comparisons indicated that while IS7-CAR killed less rapidly than m971-CAR in vitro, it remains efficient in controlling lymphoma xenograft models in vivo. Thus, IS7-CAR presents a potential alternative candidate for the treatment of refractory B-cell malignancies.

ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.

Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation.

"Built-in" PD-1 blocker to rescue NK-92 activity from PD-L1-mediated tumor escape mechanisms.

Success of adoptive cell therapy mainly depends on the ability of immune cells to persist and function optimally in the immunosuppressive tumor microenvironment. Although present at the cancer site, immune cells become exhausted and/or inhibited, due to the presence of inhibitory receptors such as PD-L1 on malignant cells. Novel genetic strategies to manipulate the PD1/PD-L1 axis comprise (i) PD-1 reversion where the receptor intracellular domain is replaced with an activating unit, (ii) the use of anti-PD-L1 CAR or (iii) the disruption of the PD-1 gene. We here present an alternative strategy to equip therapeutic cells with a truncated PD-1 (tPD-1) to abrogate PD-1/PD-L1 inhibition. We show that engagement of tPD-1 with PD-L1-positive tumor unleashes NK-92 activity in vitro. Furthermore, this binding was sufficiently strong to induce killing of targets otherwise not recognized by NK-92, thus increasing the range of targets. In vivo treatment with NK-92 tPD-1 cells led to reduced tumor growth and improved survival. Importantly, tPD-1 did not interfere with tumor recognition in PD-L1 negative conditions. Thus, tPD-1 represents a straightforward method for improving antitumor immunity and revealing new targets through PD-L1 positivity.

Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.

T cell receptor (TCR)-engineered T cell therapy is a promising cancer treatment approach. Human telomerase reverse transcriptase (hTERT) is overexpressed in the majority of tumors and a potential target for adoptive cell therapy. We isolated a novel hTERT-specific TCR sequence, named Radium-4, from a clinically responding pancreatic cancer patient vaccinated with a long hTERT peptide. Radium-4 TCR-redirected primary CD4+ and CD8+ T cells demonstrated in vitro efficacy, producing inflammatory cytokines and killing hTERT+ melanoma cells in both 2D and 3D settings, as well as malignant, patient-derived ascites cells. Importantly, T cells expressing Radium-4 TCR displayed no toxicity against bone marrow stem cells or mature hematopoietic cells. Notably, Radium-4 TCR+ T cells also significantly reduced tumor growth and improved survival in a xenograft mouse model. Since hTERT is a universal cancer antigen, and the very frequently expressed HLA class II molecules presenting the hTERT peptide to this TCR provide a very high (>75%) population coverage, this TCR represents an attractive candidate for immunotherapy of solid tumors.

Combinatorial CAR design improves target restriction.

CAR T cells targeting the B lymphocyte antigen CD19 have led to remarkable clinical results in B cell leukemia and lymphoma but eliminate all B lineage cells, leading to increased susceptibility to severe infections. As malignant B cells will express either immunoglobulin (Ig) light chain κ or λ, we designed a second-generation CAR targeting Igκ, IGK CAR. This construct demonstrated high target specificity but displayed reduced efficacy in the presence of serum IgG. Since CD19 CAR is insensitive to serum IgG, we designed various combinatorial CAR constructs in order to maintain the CD19 CAR T cell efficacy, but with IGK CAR target selectivity. The Kz-19BB design, combining CD19 CAR containing a 4-1BB costimulatory domain with an IGK CAR containing a CD3zeta stimulatory domain, maintained the target specificity of IgK CAR and was resistant to the presence of soluble IgG. Our results demonstrate that a combinatorial CAR approach can improve target selectivity and efficacy.

Protective Loop Ileostomy Closure Techniques: Comparison of Three Different Surgical Techniques.

Objective Anastomotic leaks can be very dangerous in colorectal cancers. Protective loop ileostomy is life-saving in low anterior rectal tumors to prevent pelvic sepsis. The aim of this study is to compare early morbidities for stapled, handsewn closure (end to end) or handsewn closure (anterior wall only) of loop ileostomy, and to further assess efficacy and safety for each technique.  Methods Patients who underwent loop ileostomy closure from January 2014 and December 2019 retrospectively were analyzed. Multivariate logistic regression was used to determine the effect of the potential risk factors on the rate of each complication. The patients were divided into three groups based on the anastomoses. The first group included patients who had handsewn anterior closure; the second group included patients who had side-to-side anastomosis using linear stapler, and the third group included patients who had end-to-end handsewn anastomosis. The primary endpoint of the study was the postoperative 30 days. IBM Statistical Package for the Social Sciences (SPSS), version 22.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. Results A total of 198 patients underwent reversal. There was a statistical difference between the handsewn anterior wall and stapler anastomosis in terms of postoperative ileus and wound infection. The handsewn group was superior to anastomosis with stapler (p: 0.027 and p: 0.042, respectively). A statistical difference was found between handsewn anterior wall closure and handsewn end-to-end anastomosis in terms of postoperative ileus, wound infection, and postoperative hospital stay (p: 0.013, p: 0.037, and p: 0.046, respectively). When stapled anastomosis and handsewn end-to-end anastomosis techniques were compared, a statistical difference was found in terms of postoperative ileus risk (p: 0.043), but no significant difference was found in terms of postoperative wound infection and hospital stay. Conclusions There was no significant difference in the rate of anastomotic leakage between the handsewn and stapled techniques. The rate of small-bowel obstruction was higher in the handsewn group. As a result, in this study, it was revealed that the handsewn anterior wall closure technique is the best among all ileostomy closure techniques.

How should be the Surgical Treatment Approach during the COVID-19 Pandemic in Patients with Gastrointestinal Cancer?

COVID-19 was first seen in China at the end of December 2019. COVID-19 is a novel type of coronavirus that is defined as SARS-CoV-2, which can be mild or severe in the lungs, causing acute respiratory infection. The disease was first presented in the literature as Coronavirus Disease 2019 (COVID-19) in February 2020. The disease spread rapidly and was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. There have been approximately 7734185 reported cases, and 412369 reported deaths to date (09/June/2020). As COVID-19 spread in the world and our country, hospitals struggling with this disease have also become risky areas for transmitting the disease. Health workers also have a high risk of viral contamination from direct contact of droplets and surfaces. Personal protective equipment (PPE), such as masks, coveralls, gloves, face shields and/or goggles, are mandatory. The aim is to spread the flow of cases requiring hospitalization over time, thereby preventing possible accumulation in hospitals. All non-urgent procedures, such as elective surgeries and diagnostic interventions, were significantly affected. The hospitalization procedures were mostly allocated to patients with COVID-19 infection, and surgical operations were postponed. Only urgent surgical cases and oncological surgeries that cannot be postponed were performed during this pandemic process. Patients followed by oncology are immunosuppressed both because of the disease itself and the side effects of chemotherapy and/or radiotherapy taken. This makes patients more susceptible to infections, and the prognosis of infections in these patients is worse and more destructive. Cancer patients are almost twice as likely to catch COVID-19 compared to the general population. The choice of surgical procedures and perioperative management of the patients with malignancy has become even more important in the COVID-19 pandemic. In this study, we analyzed the treatment processes of our patients with malignancy that underwent a surgical oncological procedure during this pandemic.

Colorectal cysts as a validating tool for CAR therapy.

BACKGROUND: Treatment of cancers has largely benefited from the development of immunotherapy. In particular, Chimeric Antigen Receptor (CAR) redirected T cells have demonstrated impressive efficacy against B-cell malignancies and continuous efforts are made to adapt this new therapy to solid tumors, where the immunosuppressive tumor microenvironment is a barrier for delivery. CAR T-cell validation relies on in vitro functional assays using monolayer or suspension cells and in vivo xenograft models in immunodeficient animals. However, the efficacy of CAR therapies remains difficult to predict with these systems, in particular when challenged against 3D organized solid tumors with highly intricate microenvironment. An increasing number of reports have now included an additional step in the development process in which redirected T cells are tested against tumor spheres. RESULTS: Here, we report a method to produce 3D structures, or cysts, out of a colorectal cancer cell line, Caco-2, which has the ability to form polarized spheroids as a validation tool for adoptive cell therapy in general. We used CD19CAR T cells to explore this method and we show that it can be adapted to various platforms including high resolution microscopy, bioluminescence assays and high-throughput live cell imaging systems. CONCLUSION: We developed an affordable, reliable and practical method to produce cysts to validate therapeutic CAR T cells. The integration of this additional layer between in vitro and in vivo studies could be an important tool in the pre-clinical workflow of cell-based immunotherapy.

A comparison study of left-hand three-port videoscopy, left-hand four-port videoscopy and standard four-port videoscopy in laparoscopic cholecystectomy.

A comparison study of left-hand three-port videoscopy, left-hand four-port videoscopy and standard four-port videoscopy in laparoscopic cholecystectomy AIM: Reviewing the recent publishments on the safeness and practicality of three-port cholecystectomy we aimed to introduce the results of cholecystectomy that were performed by the primary surgeon's left hand videoscopy application through three ports. MATERIAL AND METHODS: The data of 60 total laparoscopic cholecystectomy patients were retrospectively anaylsed. 20 patients underwent three-port laparoscopic cholecystectomy with videoscopy using the primary surgeon's left hand, 20 patients underwent four-port laparoscopic cholecystectomy, again with left hand videoscopy application, and the other 20 patients underwent standard four-port laparoscopic cholecystectomy by a more experienced surgeon. Kolmogorov-Smirnov test was used to evaluate the distribution normalization of parameters. To compare the parameters of multiple groups; one-way ANOVA-Tukey HSD was used for normal distributed, the Kruskal-Wallis test was used for abnormal distributed values. Pearson's chi-squared test was used for categorical values. The results with p-values of less than 0.05 were accepted as statistically significant. RESULTS: There were no differences between the groups for preoperative (p=0.456) and perioperative clinical characteristics (p=0.918), mean operation time (p=0.855), perioperative complication (p=0.153), conversion to open surgery (p=0.362) and the need for first assistant surgeon (p=0.235). However, the need for second assistant surgeon (p=0.017), assistant nurse (p=0.014) and fourth tool usage (p=0.000) were significantly lower in the three port group. CONCLUSION: Left-hand videoscopy in three-port laparoscopic cholecystectomy is reliable and effective as the conventional techniques and cheaper than conventional techniques. It's easily applicaple and learnable for experienced surgeons. KEY WORDS: Cholecystectomy, Four ports, Laparoscopy, Left-hand videoscopy, Three ports.

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma.

T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects in B-cell non-Hodgkin lymphoma (B-NHL) patients. However, a subset of patients who relapse after CD19CAR T-cell therapy have outgrowth of CD19- tumor cells. Hence, development of alternative CARs targeting other B-cell markers represents an unmet medical need for B-cell acute lymphoblastic leukemia and B-NHL. Here, we confirmed previous data by showing that, overall, B-NHL has high expression of CD37. A second-generation CD37CAR was designed, and its efficacy in T cells was compared with that of CD19CAR. In vitro assessment of cytotoxicity and T-cell function upon coculture of the CAR T cells with different target B-cell lymphoma cell lines demonstrated comparable efficacy between the 2 CARs. In an aggressive B-cell lymphoma xenograft model, CD37CAR T cells were as potent as CD19CAR T cells in controlling tumor growth. In a second xenograft model, using U2932 lymphoma cells containing a CD19- subpopulation, CD37CAR T cells efficiently controlled tumor growth and prolonged survival, whereas CD19CAR T cells had limited effect. We further show that, unlike CD19CAR, CD37CAR was not sensitive to antigen masking. Finally, CD37CAR reactivity was restricted to B-lineage cells. Collectively, our results demonstrated that CD37CAR T cells also can effectively eradicate B-cell lymphoma tumors when CD19 antigen expression is lost and support further clinical testing for patients with relapsed/refractory B-NHL.

TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma.

Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have been modest in B-cell non-Hodgkin lymphoma (NHL). Coblockade of checkpoint receptors may therefore be necessary to optimize antitumor T-cell responses. Here, characterization of coinhibitory receptor expression in intratumoral T cells from different NHL types identified TIGIT and PD-1 as frequently expressed coinhibitory receptors. Tumors from NHL patients were enriched in CD8+ and CD4+ T effector memory cells that displayed high coexpression of TIGIT and PD-1, and coexpression of these checkpoint receptors identified T cells with reduced production of IFNγ, TNFα, and IL2. The suppressed cytokine production could be improved upon in vitro culture in the absence of ligands. Whereas PD-L1 was expressed by macrophages, the TIGIT ligands CD155 and CD112 were expressed by lymphoma cells in 39% and 50% of DLBCL cases and in some mantle cell lymphoma cases, as well as by endothelium and follicular dendritic cells in all NHLs investigated. Collectively, our results show that TIGIT and PD-1 mark dysfunctional T cells and suggest that TIGIT and PD-1 coblockade should be further explored to elicit potent antitumor responses in patients with NHL.

Chimeric antigen receptor preparation from hybridoma to T-cell expression.

The successful use of chimeric antigen receptor (CAR) for hematological cancer treatment has influenced the direction taken in translational research toward an increasing focus on personalized targeted immunotherapy. Thus, a growing number of labs worldwide are now interested in testing their old antibody collections in this format to broaden the spectrum of utility and improve safety and efficacy. We herein present a straightforward protocol for the identification of an antibody from a hybridoma and the design of the single chain fragment that will be placed on the extracellular part of the CAR construct. We further show how to test the expression and the activity of the construct in primary T cells. We illustrate our demonstration with two new CARs targeted against the B cell receptor, more precisely the light chains κ and λ, that represent potential alternatives to the CD19 CAR used in the treatment of B-cell malignancies.

Treating osteosarcoma with CAR T cells.

Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5%-10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T-cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR-T treatment in a solid tumour. We will discuss the experiences with CAR-T therapy development and efficacy to combat the clinical challenges in OS.

A Spheroid Killing Assay by CAR T Cells.

Immunotherapy has become a field of growing interest in the fight against cancer otherwise untreatable. Among all immunotherapeutic methods, chimeric antigen receptor (CAR) redirected T cells obtained the most spectacular results, in particular with pediatric B-acute lymphoblastic leukemia (B-ALL). Classical validation methods of CAR T cells rely on the use of specificity and functionality assays of the CAR T cells against target cells in suspension and in xenograft models. Unfortunately, observations made in vitro are often decoupled from results obtained in vivo and a lot of effort and animals could be spared by adding another step: the use of 3D culture. The production of spheroids out of potential target cells that mimic the 3D structure of the tumor cells when they are engrafted into the animal model represents an ideal alternative. Here, we report an affordable, reliable and easy method to produce spheroids from a transduced colorectal cell line as a validation tool for adoptive cell therapy (exemplified here by CD19 CAR T cells). This method is coupled with an advanced live imaging system that can follow spheroid growth, effector cells cytotoxicity and tumor cell apoptosis.

Stercoral perforation of the rectosigmoid colon due to chronic constipation: A case report.

INTRODUCTION: Chronic constipation is very common in elderly patients. As a result of this situation fecaloma is also frequently seen at these ages. However, the stercoral perforation caused by fecaloma is a rare situation to occur. The rectosigmoid colon is the most affected colonic segment. It is seen in older patients with concomitant diseases and a low quality of life. PRESENTATION OF CASE: Here in this case, we have to report an 83 - year-old male patient who came to the emergency room with complaints of abdominal pain and constipation for two days. He had Type II Diabetes Mellitus, had a cardiac stent and also Alzheimer's disease. We diagnosed a rectosigmoid perforation due to a large fecaloma. This case presentation was prepared in accordance with the scare checklist guidelines (Agha et al., 2016 [1]). DISCUSSION: Constipation and faecal impaction are common entities, particularly in elderly and bedridden patients. Fecalomas are collections of dehydrated, hardened stool. They rarely can cause colonic ischemia and/or stercoral perforation. Stercoral perforation is the perforation or rupture of the intestine walls by a stercoraceous mass. Stercoral perforation is a very dangerous, life-threatening situation, as well as a surgical emergency, because the spillage of contaminated intestinal contents into the abdominal cavity leads to peritonitis, a rapid bacteremia with many complications. CONCLUSION: Fecalomas can cause stercoral perforations. This situation can be confused with other causes of acuteabdomen in these patients. Early surgery can be life saving.

A TCR-based Chimeric Antigen Receptor.

Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.

Benefits of xiphoidectomy in total gastrectomy: Technical note.

OBJECTIVE: The esophago-gastric junction may be challenging during total gastrectomy due to gastric cancer. This situation may compromise the security of both the dissection and anastomosis. The purpose of this study was to investigate the usefulness of xiphoidectomy to overcome this issue. MATERIAL AND METHODS: The files of patients who underwent total gastrectomy + D2 lymph node dissection due to proximal gastric cancer or cardia cancer between April 2002-December 2013 were retrospectively evaluated. We assessed the outcome in patients with xiphoidectomy in addition to the midline incision in terms of xiphoidectomy technique, xiphoidectomy time, and operative and postoperative complications. RESULTS: Thirty cases were identified to undergo xiphoidectomy. Nineteen patients were male and 11 were female, with a mean age of 51 (21-80) years. The time required for xiphoidectomy was 7-15 minutes (mean 8.7 minutes). The mean additional time required for the closure of the incision in cases with xiphoidectomy was 2 minutes. There was minimal arterial bleeding from the diaphragmatic surface in one patient, which was controlled by electrocautery. Only two patients developed wound infection. CONCLUSION: Performing xiphoidectomy is quite easy, after a certain learning phase. The operative time was 7-15 minutes longer due to excision of xiphoid and closure of the related defect. Minor hemorrhage was a problem during surgery. There were no early or late post-operative complications. We suggest that the procedure is beneficial in selected cases with requirement of a wider operative field or better exposure of the esophago-gastric junction during total gastrectomy for gastric cancer, and recommend removal of the xiphoid bone.

Solid-pseudopapillary neoplasm of the pancreas: Clinicopathologic and immunohistochemical analysis of nine cases.

BACKGROUND: Solid-pseudopapillary neoplasm (SPPN) of the pancreas is a distinctive tumor of low malignant potential with a predilection for female patients in the second and third decades of life. We studied nine cases of SPPN of the pancreas and reviewed the literature concerning these uncommon tumors. MATERIALS AND METHODS: A total of 7 cases of SPPN located in the tail of the pancreas and two located in the head of the pancreas were presented. Distal pancreatectomy in three patients and distal pancreatectomy with splenectomy in two patients Whipple's operation in four patients were performed. Histological diagnosis was made by performing hematoxylin-eosin and periodic acid-Schiff staining, immunohistochemical staining. Follow-up of the patients was between 2 months and 12 years. RESULTS: Computed tomography and magnetic resonance imaging were found as equivocal for diagnosis. Mass containing cystic and solid areas were not characteristic but raised suspicion of SPPN. Pathologic examination showed SPPN in all patients. No metastasis or recurrence was detected during follow-up. CONCLUSIONS: Solid-pseudopapillary neoplasm is a relatively rare tumor, and patients tend to survive for a long period. Preoperative imaging is not characteristic. Pathologic examination is the mainstay in the diagnosis. Complete surgical removal is the best choice of treatment.

Timing of cholecystectomy in biliary pancreatitis treatment.

OBJECTIVE: Gallstone pancreatitis constitutes 40% of all cases with pancreatitis while it constitutes up to 90% of cases with acute pancreatitis. The treatment modality in this patient population is still controversial. In this study, we aimed to compare the results of early and late cholecystectomy for patients with biliary pancreatitis. MATERIAL AND METHODS: Patients treated with a diagnosis of acute biliary pancreatitis in our clinics between January 2000 and December 2011 were retrospectively reviewed. Patients were divided into two groups: Group A, patients who underwent cholecystectomy during the first pancreatitis attack, Group B, patients who underwent an interval cholecystectomy at least 8 weeks after the first pancreatitis episode. The demographic characteristics, clinical symptoms, number of episodes, length of hospital stay, morbidity and mortality data were recorded. All data were evaluated with Statistical Package for the Social Sciences (SPSS) 13.0 for windows and p <0.05 was considered as statistically significant. RESULTS: During the last 12 years, a total of 91 patients with surgical treatment for acute biliary pancreatitis were included into the study. There were 62 female and 29 male patients, with a mean age of 57.9±14.6 years (range: 21-89). A concomitant acute cholecystitis was present in 46.2% of the patients. Group A and B included 48 and 43 patients, respectively. The length of hospital stay was significantly higher in group B (9.4 vs. 6.8 days) (p<0,05). More than half of the patients in Group B were readmitted to the hospital for various reasons. No significant difference was observed between the two groups, one patient died due to heart failure in the postoperative period in group B. CONCLUSION: In-hospital cholecystectomy after remission of acute pancreatitis is feasible. It will not only result in lower recurrence and complication rates but also shorten length of hospital stay. We recommend performing cholecystectomy during the course of the first episode in patients with acute pancreatitis.