Could we use PD-1 and PD-L1 expression on lymphocytes and monocytes as predictive markers for prognosis of acute biliary pancreatitis?

PURPOSE: This study aimed to assess the significance of immunophenotyping and serum cytokines in predicting the clinical progression of acute biliary pancreatitis (ABP). MATERIALS AND METHODS: Cytokine levels, T-helper, cytotoxic T, natural killer (NK) cells, monocytes, HLA-DR, and PD-1, as well as PDL-1 immune checkpoints, were measured in ABP patients at the time of diagnosis and compared with results from healthy volunteers. The study also compared leukocyte counts, hematocrit, immunophenotyping results, cytokine statuses, and PD-1, PDL-1 expression between healthy volunteers and ABP subgroups categorized by pancreatitis severity. RESULTS: The study included 65 ABP patients and 20 healthy volunteers. Significant differences were observed between groups in hematocrit, leukocyte counts, total monocytes, lymphocytes, CD3+ total T cells, CD4+ Th cells, PD-1 expression on CD4+ and CD8+T lymphocytes, HLA-DR expression on CD14+ monocytes, NK cells, PD-L1 expression on CD14+ monocytes, classical and intermediate monocytes, as well as levels of IL-6, IL-8, IL-10, IL-18, and IL-33 cytokines. Moderate correlations were found with lymphocyte counts, PD-1+CD4+ cells, PD-L1+CD14+ cells, and strong correlations with HLA-DR+CD14+ cells. Hematocrit, CD3+ total T cells, NK cells, CD4+PD-1 + T cells, and CD8+PD-1 + T cells showed independent associations with the severity of ABP. Lymphocyte counts, CD14+HLA-DR+ cells, CD14+PD-L1+ cells, CD4+PD-1 + T cells, classical, and intermediate monocytes exhibited the highest Area Under the Curve rates in determining organ failure. CONCLUSIONS: Hematocrit, lymphocyte counts, CD14+HLA-DR+ cells, CD14+PD-L1+ cells, and intermediate monocytes emerged as parameters most closely associated with the severity and these parameters could be useful in predicting the severity of ABP.

Predicting the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using Soluble Immune Checkpoints.

Introduction: Personalizing neoadjuvant therapy for locally advanced rectal cancer (LARC) requires identifying biomarkers that predict treatment response. This study evaluates soluble immune checkpoints (sICPs) as predictive markers for neoadjuvant treatment response in LARC patients located in the middle and lower rectum. Materials and Methods: This prospective study included patients diagnosed with clinical stage T3 or T4 rectal cancer (RC) based on pelvic magnetic resonance imaging, with or without pelvic lymph node involvement. The modified Ryan scoring system was used to assess the response to neoadjuvant chemoradiotherapy (nCRT). Blood samples were collected from all RC patients before initiating nCRT. Various sICPs (sCD25, 4-1BB, B7.2, free active TGF-ß1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, galectin-9), along with age, gender, stage, blood cell counts, and biochemical variables, were recorded and compared based on tumor regression grade (TRG). Results: Among 38 participants, lymphocyte count was higher, and platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet count were lower in patients with complete/near-complete response (TRG 0/1). In addition, TRG 0/1 patients had significantly lower levels of soluble galectin-9 than TRG 2/3 patients. Furthermore, platelet count was the only parameter that showed a significant difference among the three groups (TRG 0/1, TRG 2, and TRG 3). PLR demonstrated the highest sensitivity and specificity, with >80% for both measures. Conclusions: Lymphocyte count, PLR, NLR, platelet count, and galectin-9 may help predict favorable neoadjuvant treatment response in LARC patients, although without providing a definitive outcome. Personalized therapy based on these markers could enhance treatment decision making in LARC management.

Effect of bariatric surgery procedures on serum cytokine and Nesfatin-1 levels.

BACKGROUND: and Purpose: Obesity is known to cause chronic inflammation. We aimed to evaluate the changes in Nesfatin-1 and serum cytokine levels of patients who underwent sleeve gastrectomy or gastric bypass surgery. METHODS: A total of 30 patients with BMI>35 and undergoing bariatric surgery were divided in two group, sleeve gastrectomy (SG) (group-1), Roux-en-Y gastric bypass (RYGB) (group-2). Demographic data, weight, BMI, AST, ALT, blood glucose, CRP values, and IL-1ß, IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 cytokine, and Nesfatin-1 values were noted at the time of hospitalization and in the 6th month postoperative follow-up. RESULTS: The mean age of the patients was 37.56 ± 11.73 years, and there were 16 females and 14 males in the study. Body weight and excess body weight change were slightly higher in RYGB patients than in SG patients. In RYGB and SG patients, a significant decrease was found in glucose, AST, ALT, CRP, IL-6, IL-10, and IL-18 values compared to the preoperative period, and serum Nesfatin-1 levels were significantly increased in RYGB patients and not significantly in SG patients. There were also significant decreases in IL-1ß levels in RYGB patients. On the other hand, a decrease in cytokines was observed in both surgical methods, except for IL-17A, although it was not significant. CONCLUSION: The present study showed that there is also a regression in inflammation, which can be associated with NLRP3 inflammasome, due to weight loss after bariatric surgery, more specifically in RYGB.

The role of serum nesfatin-1 in a rat model of acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a disease that can still be fatal despite rapid advances in medicine. The relationship between serum nesfatin-1 levels and AP is still to be fully resolved. OBJECTIVES: To investigate the utility of serum nesfatin-1 levels in the diagnosis of AP. MATERIAL AND METHODS: Twenty-four male Sprague Dawley rats were divided into control, mild pancreatitis and severe pancreatitis groups (n = 8/group). Acute pancreatitis was induced by cerulein injection and the control group received saline injections. Then, the serum nesfatin-1, amylase, lipase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined. A pathologist blinded to the study scored the severity of pancreatitis. RESULTS: There was a considerable decrease in serum nesfatin-1 levels in parallel to the severity of pancreatitis, though there was no statistically significant relationship observed between pancreatitis and nesfatin-1. In addition, there was no significant difference in AST or ALT levels among the groups. However, a strong positive correlation between amylase and lipase levels was observed (p < 0.05). The severe pancreatitis group (group 3) had a higher lipase level and pathology score than mild pancreatitis group (group 2), and this difference was statistically significant. CONCLUSIONS: Serum nesfatin-1 may be used as a diagnostic and severity marker in pancreatitis in the future.

Does milk of magnesia impact length of hospital stay after major colorectal resection.

BACKGROUNDS: Milk of magnesia (MoM) has been reported to accelerate return of bowel function following surgery. However, there is insufficient evidence regarding the impact of MoM on postoperative recovery after colorectal surgery. We aimed to determine the impact of MoM on postoperative length of stay in patients undergoing colorectal surgery. METHODS: All patients who underwent colorectal resection without an ileostomy between 2015 and 2018 were included. Patients were divided into two groups based on whether postoperative MoM (MoM) was administered or not, according to surgeons' prescribing preferences. Consecutive patients of surgeons who prescribe MoM were included in the MoM group, while consecutive patients of surgeons who prefer not to prescribe MoM served as the control group. Age, gender, preoperative comorbidities, surgical approach, length of stay, readmission, postoperative complications and mortality were evaluated and compared between the groups. RESULTS: A total of 3292 patients were included; 523 (15.9%) patients were prescribed MoM. Patients in the MoM group were found to be significantly older, with higher BMI and ASA class, and more often undergoing operations for cancer resection or colostomy creations, than the control group. Postoperative complications were comparable between the groups. On multivariable linear regression, MoM use was associated with a 14.1% reduction in length of stay (MoM group 4 (2; 8), control group 5 (3; 8 P = 0.006)). CONCLUSION: MoM as adjunct medication in the postoperative period following colorectal surgery is associated with reduced length of stay, without an increase in postoperative complications.

Is Endoscopic Submucosal Dissection for Colorectal Lesions Performed in the Endoscopy Suite Safe and Cost Saving?

BACKGROUND: We aimed to compare the outcomes and the cost differences of endoscopic submucosal dissection (ESD) procedures in the endoscopy suite (ES) versus the operating room (OR). MATERIALS AND METHODS: The procedures in the OR were compared with procedures performed in the ES for demographics, lesion characteristics, procedure outcome, and procedure charges. The study included 163 procedures in the ES and 73 in the OR. RESULTS: Both were similar in age, sex, body mass index, and intraprocedural and postoperative 30-day (late) complications. ES cases had significantly greater polyp size, were more commonly right-sided polyps, and had shorter hospital stays, with similar en bloc and margin-negative resection rates. The overall cost ratio of ESD procedures in ES to OR was 0.47 ( P <0.001). CONCLUSIONS: Colorectal ESD procedures performed in the ES have similar efficacy and safety as those in the OR. Procedures performed in the ES were associated with a shorter length of stay and significant periprocedural cost savings.

Endoluminal Surgery Using a New Enabling Platform With Working Channels to Facilitate Endoscopic Submucosal Dissection in the Treatment of Complex Colorectal Lesions.

BACKGROUND: Although endoscopic submucosal dissection provides higher en-bloc resection rates for larger colorectal lesions, it has not been widely adopted because of technical difficulties. Here we present our initial experience with a novel device facilitating endoluminal surgery. IMPACT OF INNOVATION: The impact of innovation is the development of an endoluminal device increasing the utilization of the endoscopic submucosal dissection technique with higher success rates and lower complications. TECHNOLOGY MATERIALS AND METHODS: This was a single-center experimental feasibility study involving 15 patients who had undergone endoscopic submucosal dissection between August 2019 and December 2020. The DiLumen C2 device was used selectively in patients with complex colorectal lesions. PRELIMINARY RESULTS: Fifteen patients with complex colorectal lesions underwent endoscopic submucosal dissection with a mean age of 64.5 years. The mean lesion size was 40.7 mm. All patients except 1 had an R0 en-bloc endoscopic submucosal dissection resection. There were no procedural or postprocedural complications. The median length of stay was 1 day. CONCLUSION: We report the safety and feasibility of the novel endoscopic platform facilitating en-bloc resection of colorectal lesions. FUTURE DIRECTIONS: The study needs validation in larger comparative series of patients with longer follow-up.

Long-term outcomes of sporadic rectal cancer versus ulcerative colitis-associated rectal cancer: a matched case-control study.

BACKGROUND: Although patients with ulcerative colitis (UC) are at increased risk of rectal cancer compared to the general population, it remains unclear whether their oncologic outcomes are different than sporadic rectal cancer (S-RC).We aimed to compare survival and oncologic outcomes in S-RC versus UC-associated rectal cancer (UC-RC). METHODS: We performed a retrospective case-control study of patients who underwent surgical resection for rectal cancer between 2005 and 2015. Data collected included patient demographics, intraoperative variables, postoperative outcomes, and oncological outcomes. RESULTS: A total of 138 patients were included; 92 patients with S-RC and 46 with UC-RC. Both groups were comparable in terms of demographics, oncologic characteristics, oncologic treatment strategies, perioperative complications and operative factors except for preoperative radiotherapy. At a median follow-up time of 3.7 years the 3-and 5-year OS rates; the 1-and 3-year DFS rates were comparable between the groups. CONCLUSION: Ulcerative colitis-associated rectal cancer patients have similar survival and oncologic outcomes as sporadic rectal cancer patients.

The Potential Role of Model for End-Stage Liver Disease (MELD)-Sodium Score in Predicting the Severity of Acute Pancreatitis.

Background and aim Acute pancreatitis is a common inflammation of the pancreas which can be severe and even potentially mortal. High rates of mortality showed the importance of immediate identification of patients at high risk and led the clinicians to refer to various scoring systems. Our aim was to investigate a clinical predictive model using the Model for End-Stage Liver Disease-Sodium (MELD-sodium) scoring system, adapting it to acute pancreatitis patients referring to the systemic inflammatory nature of the disease and potential multi-organ failures in severe form. Methods Our multicenter study was designed retrospectively. The medical records were reviewed for the period of two years. Demographics, biochemical results, MELD-sodium scores and mortality rates were analysed. Results MELD-sodium score was found to be statistically correlated with both mortality and the severity of pancreatitis (p<0.001) and significant difference between both mild and severe (p<0.001), moderate and severe groups (p<0.001). Mortality was found to be significantly higher in patients with MELD-Na score when the cut-off value was accepted as '≥11'. Conclusion We found that MELD-sodium score was significantly associated with both severity of disease and mortality rates and also significantly effective between both mild/severe and moderate/severe groups which may be a guide for future multi-center reviews with larger patient and control groups, which can define the potential role of this non-invasive and easy-to-use predictive model in acute pancreatitis patients.

Intraoperative Colonoscopy During Colorectal Surgery Does Not Increase Postoperative Complications: An Assessment From the ACS-NSQIP Procedure-targeted Cohort.

Intraoperative colonoscopy (IOC) is an adjunct in colorectal surgery to detect the location of the lesions and assessing anastomotic integrity. The authors aimed to evaluate the safety and feasibility and postoperative morbidity of IOC in left-sided colectomy patients for colorectal cancer. Patients undergoing elective left-sided colectomy without any proximal diversion for colorectal cancer between 2013 and 2016 were reviewed from the American College of Surgeons National Surgical Quality Improvement Program procedure-targeted database. Demographics, comorbidities, short-term outcomes, and postoperative morbidity of patients were evaluated. A total of 8811 patients were identified and IOC was performed for 1143 (12.97%) patients. There was no significant difference in postoperative complications between the IOC and non-IOC groups. Patients with IOC had shorter total hospital length of stay. The use of IOC does not adversely affect short-term outcomes after colorectal resections. Surgeons may utilize IOC liberally for left-sided colorectal resections.

Giant composite pheochromocytoma and gastrointestinal stromal tumor in a patient with neurofibromatosis: A case report.

A 54-year-old male was admitted to our department with neurofibromatosis and hypertension. During his examination, a mass was detected in the abdomen, and he was transferred to a surgical clinic. At the first examination of the patient, extensive café-au-lait spots and granulomas were detected on the body and the mass occupying right abdomen quadrant was palpable. The patient's medical history indicated that he had hypertension for almost a decade. The patient also stated that nodules on the body existed from his earliest recollection and he had relatives with neurofibromatosis. The patient was taken to a surgical operation. A mass with 30×23 cm in size was removed. The area of the nodular structure, with 0.5 cm in diameter, in the stomach serosa was also removed. The tumor was composed of phaeochromocytoma in the larger spaces and ganglioneuromas in the relatively narrow spaces. The nodular area removed in gastric serosa was reported as a very low-risk gastrointestinal stromal tumor. Apart from this rare combination, adrenal mass removed from the patient was considerably larger than the masses in the literature until now. Therefore, we aimed to present this rare case with a literature background.

Modified frailty index predicts high-risk patients for readmission after colorectal surgery for cancer.

BACKGROUND: Modified frailty index (mFI) has been proposed as a reliable tool in predicting postoperative outcomes after surgery. This study aims to evaluate whether mFI could be utilized to predict readmissions after colorectal resection for patients with cancer by using nationwide cohort. METHODS: Patients undergoing elective abdominal colorectal resection for colorectal cancer were reviewed from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) procedure-targeted database (2010-2012). A previously described mFI was calculated. Demographics, comorbidities, and 30-day postoperative complications were compared between patients who were readmitted or not after colorectal surgery. RESULTS: A total of 7337 patients were identified with a mean age of 65.8(±13.6) years. Eight hundred seventy-one (11.8%) patients were readmitted at least once within 30 days. Age, gender, BMI, and other comorbidities were comparable between the groups. O approach, current smoking, mFI(>3/11), disseminating cancer, bleeding disorder and longer operative time were found to independently associated with readmission. CONCLUSIONS: An 11-point modified frailty index as measured in NSQIP correlates with readmissions after colorectal resection in patients with colon and rectal cancer.

Evaluation of the predictive power of laboratory markers in the diagnosis of acute appendicitis in the elderly.

OBJECTIVE: The aim of this study was to analyze the predictive value of preoperative laboratory findings in acute appendicitis in geriatric patients aged >65 years. METHODS: We enrolled a total of 4121 patients. A retrospective evaluation of the demographic features was made using preoperative laboratory values such as the white blood cell (WBC), neutrophil, and lymphocyte counts; platelet counts; the mean platelet volume and bilirubin values; and postoperative pathological data of the patients from the electronic file system. The neutrophil-to-WBC and neutrophil-to-lymphocyte ratios were calculated. Patients were divided into two groups, as geriatric (≥65 years old, n=140) and non-geriatric (<65 years old, n=3981). RESULTS: The white blood cell and lymphocyte counts, and the neutrophil-to-WBC ratio, were significantly higher in the non-geriatric group (p<0.001, p=0.013, and p=0.021, respectively). The neutrophil and platelet counts were higher in the non-geriatric group, but this difference was not statistically significant (p=0.073 and p=0.072, respectively). A higher neutrophil-to-lymphocyte ratio was determined in the geriatric group, but the difference was not significant (p=0.176). According to the optimumal cutoff value of 12.11×103/µL for WBC, specificity and sensitivity values of 65.4% and 57.9% were calculated, respectively; the AUC value was 0.632±0.024 (p<0.001). A receiver operating characteristic (ROC) analysis was used to calculate the optimum cutoff values of neutrophil-to-WBC ratio, lymphocyte, and the mean platelet volume, but the diagnostic accuracy of these tests was inadequate with an AUC of <0.6. CONCLUSION: WBC values >12.11×103/µL were predictive of acute appendicitis in geriatric patients. The other parameters were not predictive, and further studies are required.

May Nesfatin-1 be a Biomarker in Acute Mesenteric Ischemia?

OBJECTIVE: To investigate the diagnostic value of nesfatin-1 in cases of intestinal ischemia and ischemia/reperfusion. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: The Experimental Animals Laboratory of Bezmialem University, in June 2018. METHODOLOGY: Twenty-one healthy male Sprague Dawley rats were randomly divided into three groups of 7 rats each. In group 1: 1-hour intestinal ischemia followed by 5-hour reperfusion was performed. In group 2: rats were subjected to 6-hour intestinal ischemia. In group 3: rats underwent laparotomy and closure without performing any further procedure. Changes in leukocyte count, amylase, blood sugar, LDH, SGOT, CRP, and nesfatin-1 levels were determined. For histopathological examination, a small intestinal sample was taken and preserved in 10% formaldehyde. RESULTS: Nesfatin-1 value in group 2 was significantly higher than that in group 1 and group 3 (p=0.005, and p <0.001 respectively). Nesfatin-1 value in group 1 was significantly higher than that in group 3. A significant (r = 0.864/p <0.001) positive correlation was observed between nesfatin-1 value and pathology score. The pathology score of group 2 was significantly higher than that of group 1 and group 3 (p <0.001). CONCLUSION: Serum nesfatin-1 can be a biomarker in acute mesenteric ischemia.

Effect of Dexketoprofene Trometamol on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVE: To evaluate the efficacy of dexketoprofene trometamol solution following the administration of contrast agent for Endoscopic Retrograde Cholangiopancreatography (ERCP) in decreasing the rate of pancreatitis, in experimental rat model. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Faculty of Medicine, Research and Animal Laboratory of Bezmialem University, Istanbul, Turkey in January 2018. METHODOLOGY: Forty Wistar-Albino® male rats of 250-300g were divided into 4 equal groups. Group I underwent cannulation; group II had cannulation with saline; group III had cannulation and contrast agent; group IV had cannulation with contrast agent and dexketoprofene trometamol intra-muscular (IM). Twenty four hours following the procedure, the rats were sacrified and pancreatic tissues were examined histopathologically, with evaluation of blood levels of leukocyte, glucose, SGOT, LDH, amylase, and C-reactive protein (CRP) level. Histopathological grading of acute pancreatitis was performed using haematoxylin and eosin staining. RESULTS: Mean levels of amylase and leukocyte were found to be significantly higher in groups II, III, IV when compared to group I (p=0.001). CRP level was found to be highest in group III (p=0.001). Histopathological grade of pancreatitis was found to be significantly higher in groups II, III, IV than group I (p: 0.001, 0.001, 0.028, and 0.001, respectively). Scores of edema, acinar necrosis, inflammation and perivascular infiltration of group III were higher than in group IV (p=0.001). CONCLUSION: Intra-muscular administration of dexketoprofen trometamol during ERCP procedure may be beneficial in decreasing the rate of post-ERCP pancreatitis, as shown by histopathological and laboratory profile.

Effects of alpha-tocopherol on acute pancreatitis in rat.

BACKGROUND: Acute pancreatitis is a disease with high morbidity and mortality, despite all the advances in technology. The overall mortality rate of acute pancreatitis is 10%, whereas the mortality rate in infected necrotizing pancreatitis is approximately 35%. In this study, we aimed to establish acute pancreatitis in rats in order to try out the alpha-tocopherol treatment protocol and to reveal the results biochemically and histopathologically. METHODS: Twenty-four male male Sprague-Dawley rats weighing between 300 and 350 g were used in the study. In Group 1, 80 µg/kg of normal saline was subcutaneously injected into eight rats; in Group 2, 80 µg/kg of cerulein was subcutaneously injected into eight rats; and in Group 3, 80 µg/kg of cerulein was subcutaneously injected into eight rats. In addition, 30 mg/kg of alpha-tocopherol was intraperitoneally injected into eight rats. RESULTS: The mean Schoenberg score, serum amylase, and lipase and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels were statistically significantly higher in Group 2 than in Group 1. The mean Schoenberg score and serum amylase and lipase levels were statistically significantly lower in Group 3 than in Group 2. CONCLUSION: In this experimental study rat model of cerulein-induced acute pancreatitis, 30 mg/kg of alpha-tocopherol was injected intraperitoneally to examine its effect on pancreatitis. The improvement was observed in the histopathological examination of pancreatic tissues. We think that alpha-tocopherol may have a therapeutic effect on pancreatic tissue.

Stent experiences in emergency conditions in acute mechanical intestinal obstruction caused by colorectal cancer.

INTRODUCTION: Stent treatment can be applied to avoid surgery in surgically risky patients or to turn a high-risk emergency operation into a lower-risk elective operation and save time. AIM: In this study, the techniques, clinical efficacy, safety and complications of endoscopic stents applied in emergency conditions were evaluated in patients with acute mechanical intestinal obstruction (AMIO) due to colorectal cancer. MATERIAL AND METHODS: Between 2013 and 2015, 23 patients with an average age of 69.5 ±13.5 years who presented with AMIO and anastomosis stenosis secondarily to cancer to the emergency department were subjected to stent treatment under emergency conditions. RESULTS: Thirteen (56.5%) patients were diagnosed with colon cancer, 5 (21.7%) with rectal cancer, and 5 (21.7%) with stenosis in the previous anastomosis line. Fourteen (60.9%) patients were diagnosed with stage 4 cancer, 7 (30.4%) with stage 3 cancer and 2 (8.7%) with stage 2 cancer. The stents were applied to the sigmoid colon in 10 (43.5%) patients, to the recto-sigmoid area in 9 (39.1%) patients and to the rectum area in 4 (17.4%) patients. While 14 (60.9%) patients had local or locally advanced disease, 9 (39.1%) patients had metastases in different parts of their bodies, particularly in their livers. CONCLUSIONS: The study demonstrates that stents offer a favorable therapeutic alternative to emergency surgery and are associated with promising short-term outcomes as well as an acceptable safety profile for AMIO.

The Effects of Local and Systemic Administration of Proline on Wound Healing in Rats.

Purpose: Wound healing consists of a sequence of complex molecular and cellular events. Collagen is composed mainly of proline and hydroxyproline. Proline and hydroxyproline constitute 1/3 of the amino acids in collagen, which makes up approximately 30% of the proteins within the body. The hydroxylation of proline found in collagen determines the stability of the triple helical structure of collagen. In this study, we examined the effects of local and systemic administration of proline on wound healing. Materials and Methods: 24 female Sprague-Dawley rats were used in the study and divided into three groups. Group 1: The defect created in the backs of the subjects was left to secondary healing. Group 2: 200 µl proline per day was administered topically for 30 days on the defect in the backs of the subjects. Group 3: 200 µl per day was administered intraperitoneally for 30 days on the defect in the backs of the subjects. Results: On day 21, there was a statistically significant difference between the groups in terms of the mean re-epithelialization score. On days 7 and 14, there was a statistically significant difference between the groups in terms of the mean granulation score. On days 7, 14, and 21, there was a statistically significant difference between the groups in terms of the mean collagen accumulation score. On day 30, there was a statistically significant difference between Groups 1 and 3 in terms of the mean E-mode score on mechanical tensile test. Conclusion: Our study confirmed that proline has positive effects on wound healing. However, it revealed that systemic administration of proline is more effective than local administration of proline.