Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential therapeutic approach.

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8+ , CD4+ , CD4+ CD25+ CD127- ) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-ß before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4+ IFN-γ+ (p = 0.032), CD4+ TNF-α+ (p = 0.028), and the CD8+ TNF-α+ (p = 0.012) T cells. In contrast, significant decreases in CD4+ IL-10+ (p = 0.047) and CD8+ IL-10+ T cells (p = 0.022) and CD4+ CD25+ CD127-//low Treg cells secreting TGF-ß (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3- CD16+ CD56+ natural killer cells (p = 0.0027) and decreased CD19+ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-ß expression in CD4+ CD25+ CD127- Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.

Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy.

BACKGROUND: Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS: PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS: Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS: Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.

Intraoperative palpation of sentinel lymph nodes can accurately predict axilla in early breast cancer.

Recent randomized trials have shown that completion axillary lymph node dissection (ALND) is not required in all patients with a positive sentinel lymph node (SLN) who will receive radiation therapy. Although routine intraoperative pathologic assessment (IPA) becomes unnecessary and less indicated by breast surgeons in the United States and some European countries, it is still widely used all around the world. In this prospective study, the feasibility of intraoperative nodal palpation (INP) as opposed to IPA of the SLN has been analyzed. Between March 2014 and June 2015, 305 patients with clinical T1-2/N0 breast cancer from two different breast clinics (cohort A; [n = 225] and cohort B; [n = 80]) who underwent any breast surgery with sentinel lymph node biopsy (SLNB) were included in this study. Surgeons evaluated the SLNs by manual palpation before sending for IPA, and findings compared with the final pathology. The positive predictive values (PPV) of INP and IPA were 81.8% and 97.9%, respectively, whereas the negative predictive values (NPV) of INP and IPA were 83% and 92.4%. The accuracies of INP and IPA were 82.6% and 94.1%, respectively. If patients with SLNB including micrometastasis were also considered in the final pathologic assessment (FPA) (-) group that would not require a further axillary dissection, the revised NPV of INP and FPA were found to be 92.6% and 98.1%, respectively. The revised accuracy of INP also found to be increase to 86.9%. Our study, which is the only prospective one about palpation of dissected SLNs in the literature, suggests that INP can help to identify patients who do not need ALND, which encourages omitting IPA in cT1-2 N0 breast cancer.

Improved False-Negative Rates with Intraoperative Identification of Clipped Nodes in Patients Undergoing Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy.

BACKGROUND: Identification and resection of a clipped node was shown to decrease the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for patients presenting with initially node-positive breast cancer. METHODS: Between March 2014 and March 2016, a prospective trial analyzed 98 patients with axilla-positive locally advanced breast cancer (T1-4, N1-3) to assess the feasibility and efficacy of placing clips into most suspicious biopsy-proven node. The study considered blue, radioisotope active, and suspiciously palpable nodes as sentinel lymph nodes (SLNs). RESULTS: The SLN identification rate was 87.8%. The median age of the patients with an SLNB (n = 86) was 44 years (range 28-66 years). Of these patients, 77 (88.4%) had cT1-3 disease, and 10 (11.6%) had cT4 disease. The majority of the patients (n = 66, 76.7%) had cN1, whereas 21 patients (23.3%) had cN2 and cN3. A combined method was used for 37 patients (43%), whereas blue dye alone was used for the remaining patients (57%). The clipped node was the SLN in 70 patients (81.4%). For the patients with cN1 before NAC, the FNR was found to be 4.2% (1/24) when the clipped node was identified as an SLN. However, the FNR was estimated to be as high as 16.7% (1/6) for the patients with cN1 before NAC when the clipped node was found to be a non-SLN. CONCLUSIONS: The study results also suggest that axillary dissection could be omitted for patients presenting initially with N1 disease and with a negative clipped node as the SLN after NAC due to the low FNR.

Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study.

AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy.

New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer.

BACKGROUND: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. METHOD: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]). CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.

Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis.

Background: Autoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM. Methods: Patients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B). Results: The median age was 33 years (range, 24-45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12-35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26 weeks in cohort A vs. 12 weeks in cohort B; p = 0.001). Conclusion: Systemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.

A New Era in Minimally Invasive Liver Resection (MILR) Single-Incision Laparoscopic Liver Resection (SIL-LR): The First Two Cases.

Laparoscopy has gained a place in everyday surgical routine as an alternative surgical approach that decreases morbidity and postoperative hospitalization. Single port laparoscopic surgery has been introduced as a further development of laparoscopy. The feasibility and safety of single port laparoscopy is under extensive evaluation in specialized laparoscopic centers. Nevertheless, wide acceptance of the technique requires adequate documentation of the advantages of the approach over conventional laparoscopy and further refinement of surgical instrumentation to overcome intraoperative ergonomic problems.

Prospective randomized comparison of clinical results between hand-assisted laparoscopic and open splenectomies.

BACKGROUND: Although some studies have compared laparoscopic and hand-assisted laparoscopic splenectomy (HALS) in splenomegaly cases, no study has analyzed the differences between HALS and open splenectomy (OS). This study aimed to compare the HALS and OS techniques in splenomegaly cases. METHODS: This prospective study included 27 patients undergoing splenectomy for splenic disorders at the Department of General Surgery, Istanbul Medical Faculty between February and October 2007. Open splenectomy was performed for 14 patients and HALS for the remaining 13 patients. RESULTS: The end points compared included incision length, operative time, intraoperative blood loss, postoperative drain output and duration, postoperative pain scores, length of postoperative hospitalization, and perioperative complications. The authors found benefits of HALS over OS for incision length, postoperative pain score, postoperative drain output and duration, and hospital stay. The main advantages of the HALS technique over OS were less postoperative pain (p = 0.0002), shorter hospital stay (p = 0.004), and shorter abdominal incision (p = 0.012). CONCLUSIONS: For splenomegaly, HALS significantly facilitates the surgical procedure and reduces the hospital stay while maintaining the advantages of OS such as tactile sense as well as easy and atraumatic manipulation of enlarged spleens.

Single incision laparoscopic pancreas resection for pancreatic metastasis of renal cell carcinoma.

BACKGROUND: Transumbilical single incision laparoscopic surgery (SILS) offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. Herein, we report the first transumbilical single incision laparoscopic pancreatectomy case in a patient who had renal cell cancer metastasis on her pancreatic corpus and tail. METHODS: A 59-year-old female who had metastatic lesions on her pancreas underwent laparoscopic subtotal pancreatectomy through a 2-cm umbilical incision. RESULTS: Single incision pancreatectomy was performed with a special port (SILS port) and articulated equipment. The procedure lasted 330 minutes. Estimated blood loss was 100mL. No perioperative complications occurred. The patient was discharged on the seventh postoperative day with a low-volume (20mL/day) pancreatic fistula that ceased spontaneously. Pathology result of the specimen was renal cell cancer metastases. CONCLUSION: This is the first reported SILS pancreatectomy case, demonstrating that even advanced surgical procedures can be performed using the SILS technique in well-experienced centers. Transumbilical single incision laparoscopic pancreatectomy is feasible and can be performed safely in experienced centers. SILS may improve cosmetic results and allow accelerated recovery for patients even with malignancy requiring advanced laparoscopic interventions.

Is laparoscopic splenectomy safe in patients with immune thrombocytopenic purpura and very low platelet count? A single-institution experience.

PURPOSE: Minimal invasive procedures has become increasingly popular during the last decades. The aim of this retrospective study was to evaluate the safety and feasibility of laparoscopic splenectomy in patients with immune thrombocytopenic purpura who has very low platelet counts. METHODS: Between March 28, 2005 and June 08, 2013, a total of 132 patients with the diagnosis of immune thrombocytopenic purpura were included to study. The patients who underwent laparoscopic splenectomy were alienated into two groups according to their platelet counts lower than 10000 (group 1) and higher than 10000 (group 2) RESULTS: There were 16 patients in group 1 with very low platelet counts, and 116 in group 2. One patient in group 1 had converted to laparotomy due to peroperative bleeding, and there were 5 conversion to open in group 2. There were also 2 patients in group 2 who underwent laparatomy on post operative day 1 due to delayed intra-abdominal bleeding. Moreover, one patient in each group had pancreatic fistula. CONCLUSIONS: Laparoscopic splenectomy is a safe technique in patients with ITP even the patients have very low platelet counts. KEY WORDS: ITP, Laparoscopy, Low platelet count, Splenectomy.

Favorable Long-Term Outcome in Male Breast Cancer.

OBJECTIVE: Male breast cancer (MBC) is a rare type of cancer in the breast cancer series and in the male population. Data is usually extrapolated from female breast cancer (FBC) studies. We aim to study the clinicopathological characteristics and outcome of MBC patients at our institution and we aim to emphasize the differences compared with FBC. MATERIALS AND METHODS: Between January 1993 and April 2016, 56 male patients who were diagnosed as breast cancer and underwent surgical operation were retrospectively analyzed. Patients were evaluated for demographical characteristics, surgery type, clinicopathological characteristics, adjuvant and neoadjuvant treatments, follow-up time, overall survival (OS), disease free survival (DFS), and disease specific survival (DSS). RESULTS: The ratio of MBC among all breast cancers at our institution is 1%. The median age was 64 (34-85). Surgical procedures were modified radical mastectomy (MRM) in 41 patients (77%), simple mastectomy in 11 patients (21%), and lumpectomy in 1 patient (2%). Two patients were Stage 0 (4%), 7 were Stage 1 (13%), 12 were Stage 2 (22.6%), and 32 were Stage 3 (60.4%). Molecular subtypes of the invasive tumors were luminal A in 40 (80%), luminal B in 6 (12%), HER-2 type in 1 (2%), and basal-like in 3 (6%). Median follow-up time was 77 (3-287) months. 5-year and 10-year OS, DFS, and DSS rates were 80.7%, 96%, 95.6% and 71.6%, 81.9%, 91.7% respectively. CONCLUSION: MBC presents different clinicopathological and prognostic factors when compared to FBC. Our survival rates are higher than the average presented in available literature. Because of the high rate of hormone receptor positivity, hormonal therapy is the mainstay for the treatment of estrogen receptor (ER)+ male breast cancer.

Handheld gamma probe used to detect accessory spleens during initial laparoscopic splenectomies.

BACKGROUND: Preoperative determination of the accessory spleen still is a major factor in the failure of both laparoscopic and conventional techniques. This study aimed to evaluate the practicability and efficacy of a handheld gamma probe in identifying accessory spleens at the initial intervention. METHODS: This study evaluated 17 patients undergoing laparoscopic splenectomy attributable to benign hematologic disorders. All the patients had preoperative ultrasonography, computed tomography (CT) scan, and nuclear scintigraphic examination of the abdominal cavity to assess the size of the spleen, and to determine the existence of the accessory spleen or spleens. For all the patients, a handheld gamma probe count was used intraoperatively as an adjuvant method to define the presence and location of the accessory splenic tissue. Control nuclear scintigraphic examinations of all the patients were performed 1 month after the surgical procedure. RESULTS: In two cases, intraoperatively accessory splenic tissue was detected by gamma probe, confirming the preoperative CT findings for the patients. One of these patients had three accessory spleens, although preoperative CT scan showed only two of them. However, by the help of the gamma probe, a third spleen located retroperitoneally was defined. For two patients, laparoscopic exploration and handheld gamma probe count did not identify any accessory splenic tissue, although preoperative CT scan indicated accessory spleens. For detecting accessory splenic tissue, the sensitivities of the studied techniques were 0% for ultrasonography, 75% for CT scan, 0% for preoperative nuclear scintigraphy, 75% for laparoscopic exploration, and 100% for perioperative gamma probe examination. CONCLUSION: Preoperative imaging methods for accessory spleen determination still have limited benefits because of their limited sensitivity. Thus, the handheld gamma probe technique may be an adjuvant method for laparoscopic exploration ensuring that no accessory splenic tissue is missed during the initial surgical treatment of benign hematologic disorders.

Laparoscopic treatment of a wandering spleen causing partial colonic obstruction: report of a case.

Wandering spleens are rarely encountered ectopic localizations of the spleen. They are either congenital or acquired owing to the lack of or weakening of the major splenic ligaments. Herein, we present a female patient who was admitted to our hospital with the complaint of abdominal distension and chronic constipation. We performed laparoscopic splenectomy in this case for the diagnosis of a wandering spleen located in the right upper quadrant. The accepted treatment of this pathology is splenopexy unless there is no necrosis of the organ. Minimal invasive procedures should be the primary choice in the treatment of this entity.

Minimally invasive distal pancreatectomy A retrospective review of 30 cases.

OBJECTIVES: Pancreatic surgery has been greatly influenced by the advent of laparoscopic surgery and increasing experience in its performance and by advances in techniques and surgical devices. This study aimed to represent two centers' initial experiences in laparoscopic distal pancreatic surgery. METHODS: This study was a bi-centric study including 30 patients undergoing distal pancreatectomy for pancreatic disorders. All the patients were operated on from November 2006 to November 2013 in Turkey and Spain. RESULTS: Laparoscopic spleen-preserving distal pancreatectomy was performed in 9 patients, laparoscopic distal pancreatectomy was performed in 14 patients, laparoscopic enucleation was performed in 4 patients, and single-incision laparoscopic distal pancreatosplenectomy with splenectomy was performed in 3 patients. CONCLUSIONS: Laparoscopic distal pancreatectomies for pancreatic disorders are feasible and safe procedures if performed by experienced laparoscopic surgeons. KEY WORDS: Laparoscopy, Pancreas, Multi-port, Tumor, SILS.

Minimally invasive surgery in the treatment of splenosis.

Splenosis has been serious etiologic reason in the recurrence of benign hematologic diseases after elective open or laparoscopic splenectomy. Although, the incidence of splenosis in patients splenectomized for trauma is high, as long as they are asymptomatic, they do not require surgical treatment. Herein, we report a case of idiopathic thrombocytopenic purpura recurrence due to splenosis 5 years after the initial laparoscopic splenectomy. Laparoscopic treatment of splenosis was performed successfully.

Laparoscopic surgery of the splenic artery and vein aneurysm with spontaneous arteriovenous fistula.

Visceral artery aneurysms are rare and important vascular entities due to the quarter of all cases presented as surgical emergency. Nevertheless, splenic artery aneurysm (SAA) is the most common visceral and third most common intra-abdominal artery aneurysm after aorta and iliac artery. SAA accompany splenic vein aneurysm because arteriovenous fistula communication between them is a very rare entity. Location and size of the SAA determine the likelihood of rupture. Women of child-bearing age who have SAAs are at particularly high risk of death as a result of aneurysm rupture and should be treated with elective repair. Herein, we report a case of a splenic artery and vein aneurysm with arteriovenous fistula in a 25-year-old young female patient who presented with left upper quadrant pain. Diagnosis was established by computerized tomography angiogram. The patient underwent laparoscopic resection of splenic artery and vein, as well as with splenectomy. Laparoscopic therapy for SAA should be considered for the patient with a low periprocedural morbidity at experienced surgical clinics.

SILS Incisional Hernia Repair: Is It Feasible in Giant Hernias? A Report of Three Cases.

Aim. Three incisional ventral abdominal wall hernias were repaired by placing a 20 × 30 cm composite mesh via single incision of 2 cm. Methods. All three cases had previous operations and presented with giant incisional defects clinically. The defects were repaired laparoscopically via single incision with the placement of a composite mesh of 20 × 30 cm. Nonabsorbable sutures were needed to hang and fix the mesh only in the first case. Double-crown technique was used in all of the cases to secure the mesh to the anterior abdominal wall. Results. The mean operation time was 120 minutes. The patients were mobilized and led for oral intake at the first postoperative day. No morbidity occurred. Conclusion. Abdominal incisional hernias can be repaired via single incision with a mesh application in experienced centers.

Pure SILS Floppy Nissen Fundoplication with Hiatal Repair: A Case Report.

Background. Single-incision laparoscopic surgery has recently became popular on behalf of inventing less invasive procedures. In this paper, we present a case of Pure SILS Nissen Fundoplication. Patient and Methods. In February 2010 a 29-year old male patient with a 4 cm sliding hiatus hernia presenting with reflux symptoms had undergone a standard floppy Nissen Fundoplication with a hiatus repair via single 2 cm incision in umbilicus. Results. The procedure had obeyed the standard natural orifice surgery rules, and no needlescopic assistance for any stage of the operation was used so to be a pure single-incision procedure. The operation lasted for 120 minutes without any need of conversion, and the patient was discharged the following day of operation. Conclusion. In the recent time, hybrid single incision laparoscopy techniques have been defined with the use of extra-abdominal supplements for retraction of liver or stomach for Nissen procedure. In addition the main issue in single-incision upper GI and/or hiatus surgery is still the retraction of liver. We succeeded to retract the left lobe of liver through the incision and completed the operation without any need for supplemental access besides the umbilical incision till the end. SILS Hiatus Surgery can be safely and effectively done but the issue needs further clinical studies to state the efficacy when compared to standard laparoscopy.