Neutrophil to Lymphocyte Ratio in Patients Who Received Neoadjuvant Treatment before Gastrectomy.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR. OBJECTIVES: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer. METHODS: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival. RESULTS: For 124 patients the median follow-up was 23 months (range 1-88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS. CONCLUSIONS: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Management of Acute Appendicitis during the COVID-19 Pandemic: A Single Tertiary Center Experience.

BACKGROUND: The coronavirus disease-2019 (COVID-19) outbreak had an effect on healthcare. OBJECTIVES: To evaluate the presentation and management of patients with acute appendicitis. METHODS: A retrospective study was conducted of all patients presenting with acute appendicitis to the emergency department of a large tertiary center during March and April 2020. Clinical features, diagnostic workup, and management were compared. RESULTS: Seventy-four patients presented with acute appendicitis during the pandemic compared to 60 patients during the same time the year before. There were no significant differences in patient demographics: age (P = 0.65), gender (P = 0.73), smoking status (P = 0.48). During COVID-19 patients were more likely to complain of right lower quadrant pain (100% vs. 78.3%, P < 0.01). Rates of surgical treatment was similar (83.8% vs. 81.7%, P = 1); mean operative time was longer during COVID-19 (63 ± 23 vs. 52 ± 26 minutes, P = 0.03). There were no significant differences in intra-operative findings including the presence of appendiceal perforation (16.3% vs. 14.5%, P = 0.8), abscess (6.1% vs. 9.7%, P = 0.73), or involvement of cecum or terminal ileum (14.28% vs. 19.63%, P = 1). Postoperative treatment with antibiotics was more prevalent during COVID-19 (37.1% vs. 18%, P = 0.04). Length of stay (1.82 ± 2.04 vs. 2.74 ± 4.68, P = 0.2) and readmission rates (6% vs. 11.3%, P =0.51) were similar. CONCLUSIONS: The COVID-19 pandemic did not significantly affect the presentation, clinical course, management, and outcomes of patients presenting with acute appendicitis.

Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer.

BACKGROUND: Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. METHODS: A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. RESULTS: The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. CONCLUSIONS: The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.

Perineal Stapled Rectal Prolapse Resection in Elderly Patients: Long-term Follow-up.

BACKGROUND: Full-thickness rectal prolapse has a significant negative impact on quality of life. The therapeutic options, specifically in elderly patients, are imperfect. Perineal stapled rectal prolapse resection is a novel operation for treating external rectal prolapse. Long-term follow-up following this procedure is lacking. In our study, we report a long-term follow-up of 30 patients, analyzing the long-term recurrence rate, morbidity, and functional outcome. OBJECTIVE: This study aimed to examine the long-term results of perineal stapled rectal resection in a population unfit for prolonged general anesthesia. DESIGN: This was a cohort study with a prospective follow-up. SETTINGS: This study was conducted at a single tertiary referral center. PATIENTS: Patients undergoing perineal stapled rectal resection from January 2010 to June 2013 were included. INTERVENTIONS: Perineal stapled rectal prolapse resection was performed. MAIN OUTCOME MEASURES: The primary outcome measured was prolapse recurrence. RESULTS: A total of 30 patients underwent the surgical intervention. The median follow-up period was 61 months (range, 37-65). No intraoperative or postoperative complications occurred. Six patients (20%) had recurrent rectal prolapse, and continence was not achieved in any of the patients. Two patients who had recurrence underwent a redo perineal stapled rectal resection. LIMITATIONS: This study was limited by the small cohort of selected patients. CONCLUSIONS: Frail patients that can only endure a short procedure under regional anesthesia should be considered for perineal stapled rectal prolapse resection. The lack of mortality and morbidity, specifically in this population, along with the low long-term recurrence rates, make this a favorable surgical alternative. See Video Abstract at http://links.lww.com/DCR/A745.

Risk Factors for Complications of Total/Subtotal Gastrectomy for Gastric Cancer: Prospectively Collected, Based on the Clavien-Dindo Classification System.

BACKGROUND: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean). OBJECTIVES: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications. METHODS: We analyzed all gastrectomies for gastric cancer performed 2009-2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification. RESULTS: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05). CONCLUSIONS: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Laparoscopic subtotal gastrectomy for gastric cancer.

BACKGROUND: The use of laparoscopy in the treatment of gastric malignancy is still controversial. However, several reports suggest that the laparoscopic approach may be safe and applicable. The aim of this study was to review our experience with laparoscopic gastrectomy for gastric malignant tumors amenable to subtotal gastrectomy, and assess the oncologic outcome. METHODS: The laparoscopic approach to subtotal gastrectomy was selected according to both the surgeon's and patient's preference. Data regarding demographics, operative procedures, postoperative course, and follow-up were prospectively collected in a computerized database. Survival data were obtained from the national census. RESULTS: Twenty patients were operated on, 18 for gastric adenocarcinoma, one for gastric lymphoma, and one for gastrointestinal stromal tumor. There were 10 males and 10 females, mean age of 67. D1 subtotal gastrectomy with Billroth-2 reconstruction was performed. Mean operative time was 335 minutes. Tumor-free margins were obtained in all cases, and a mean of 15 lymph nodes were retrieved. Median postoperative hospital stay was 12 days. Postoperative complications included leak from the duodenal stump (2), intraabdominal abscess (2), anastomotic leak (1), wound infection (1), and bowel obstruction (1); re-operation was required in 4 patients. No perioperative mortality occurred in our series. Pathology showed nodal involvement in 8 patients. During a mean follow-up of 39 months, 4 patients expired from recurrent and metastatic disease; all had positive lymph nodes. The Kaplan-Meier calculated 5-year survival was 79%. CONCLUSION: Although a challenging and lengthy procedure, laparoscopic subtotal gastrectomy yields acceptable surgical and oncologic results that may further improve with increased surgeon experience. Thus, the application of laparoscopy in the surgical treatment of distal gastric malignancy may be considered; however, further data are needed before this approach can be recommended.

Modified Doppler-guided laser procedure for the treatment of second- and third-degree hemorrhoids.

BACKGROUND: Hemorrhoids are a common anorectal condition with a major medical and socioeconomic impact. Owing to the high incidence of symptomatic hemorrhoids in the adult population together with the risk of complications of traditional surgery, researchers are seeking less invasive methods of hemorrhoidal treatment.The aim of this study was to present our experience with the mini-invasive Doppler guided hemorrhoidal laser procedure (HeLP) in symptomatic 2nd and 3rd degree hemorrhoids with absent or minimal mucosal prolapse. METHODS: The cohort included 62 patients with symptomatic hemorrhoids who underwent the HeLP at a tertiary medical center in 2014-2016. Data were collected on clinical and perioperative characteristics and outcome. Findings were compared between patients with second- and third-degree hemorrhoids. RESULTS: The cohort included 41 male and 21 female patients of mean age 41.5 years. Fifty-one had bleeding and 11 had hemorrhoidal syndrome. Mean operative time was 16.6 ± 3.7 minutes. A total of 8-12 arterial branches were treated. Patients were discharged home within a mean of 91.95 ± 20.48 minutes and allowed to resume normal activities. Compared to patients with second-degree hemorrhoids, patients with third-degree hemorrhoids had a significantly higher rate of recto-anal repair (18.2% vs 0, p < 0.05), intraoperative bleeding (11.3% vs 5%, p < 0.05), and thrombus formation in the hemorrhoids (11.3 % vs 0, p < 0.01). At the six-month follow-up, no complications were reported, and there was significant improvement in symptoms.Using the visual analog scale, no pain was reported by 82.3% of patients at one week after surgery and 95.2% of patients at one month after surgery. CONCLUSION: Patients with hemorrhoids treated with Doppler-guided laser had an excellent outcome in terms of resolution of symptoms and postoperative pain. Only Minor short-term complications were noted. Doppler-guided laser seems to be an effective and painless technique for the treatment of symptomatic second- to third grade hemorrhoids with minimal mucosal prolapse.

[Laparoscopic colon and rectal surgery--after ten years and 350 operations].

BACKGROUND: Within a decade since laparoscopy was used in cholecystectomy it has become the preferred approach in many abdominal procedures. Laparoscopic colon and rectal surgery has not yet been adopted by the majority of surgeons, due to technical complexity and reservation regarding its oncological safety. As data and experience accumulate, this attitude is gradually changing. We present our experience with laparoscopic surgery of the large bowel over the last ten years. AIM: To assess the short and intermediate term results after laparoscopic colon and rectal surgery, and to summarize the long term results after curative colectomy for malignancy. METHODS: Data regarding all patients undergoing laparoscopic colon and rectal surgery was prospectively entered into a computerized database, including demographics, surgical technique and perioperative course. Follow-up information was gathered at outpatient clinic visits, and using telephone interviews in selected cases. Data analysis was performed using a statistical software package. RESULTS: Over a period of ten years, 350 various laparoscopic colon and rectal procedures were performed, for both benign and malignant conditions. Sixty percent of the operations were for treatment of colorectal cancer. In 14.5% of cases conversion to open laparotomy was required. Post-operative complications included surgical site infection in 17.4%, anastomotic leak in 6.9%, and a mortality rate of 2.8%. Long term follow-up revealed cancer recurrence locally in 2.3% and systemically in 8.2%. Five year survival was 56% after resection of colorectal cancer regardless of the stage, and 63% after resection with curative intent. CONCLUSIONS: The laparoscopic approach to large bowel surgery enables short and long term results comparable with those achieved by open technique, regarding perioperative complication rate and long term oncologic outcome. The advantages of laparoscopy, related to reduced abdominal wall trauma, justify the adoption of this technique as a legitimate alternative to the open approach.

RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients.

PURPOSE: The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). METHODS: An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death. RESULTS: Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%. CONCLUSIONS: The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785.

Diffusion tensor magnetic resonance imaging of the pancreas.

PURPOSE: To develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues. MATERIALS AND METHODS: Twenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients' scans. Image processing at pixel resolution yielded parametric maps of three directional diffusion coefficients λ1, λ2, λ3, apparent diffusion coefficient (ADC), and fractional anisotropy (FA), as well as a λ1-vector map, and a main diffusion-direction map. RESULTS: DTI measurements of healthy pancreatic tissue at b-values 0,500 s/mm² yielded: λ1 = (2.65±0.35)×10⁻³, λ2 = (1.87±0.22)×10⁻³, λ3 = (1.20±0.18)×10⁻³, ADC = (1.91±0.22)×10⁻³ (all in mm²/s units) and FA = 0.38±0.06. Using b-values of 100,500 s/mm² led to a significant reduction in λ1, λ2, λ3 and ADC (p<.0001) and a significant increase (p<0.0001) in FA. The reduction in the diffusion coefficients suggested a contribution of a fast intra-voxel-incoherent-motion (IVIM) component at b≤100 s/mm², which was confirmed by the multi-b DWI results. In PDACs, λ1, λ2, λ3 and ADC in both 0,500 s/mm² and 100,500 s/mm² b-values sets, as well as the reduction in these diffusion coefficients between the two sets, were significantly lower in comparison to the distal normal pancreatic tissue, suggesting higher cellularity and diminution of the fast-IVIM component in the cancer tissue. CONCLUSION: DTI using two reference b-values 0 and 100 s/mm² enabled characterization of the water diffusion and anisotropy of the healthy pancreas, taking into account a contribution of IVIM. The reduction in the diffusion coefficients of PDAC, as compared to normal pancreatic tissue, and the smaller change in these coefficients in PDAC when the reference b-value was modified from 0 to 100 s/mm², helped identifying the presence of malignancy.