Indocyanine Green Is a Safe and Effective Alternative to Radioisotope in Breast Cancer Sentinel Lymph Node Biopsy regardless of Patient Body Mass Index.

INTRODUCTION: A recent meta-analysis [Lancet Oncol. 2010;11:908-909] has confirmed high sensitivity of indocyanine green (ICG) fluorescence mapping for sentinel node detection in early breast cancer. Concerns have previously been raised regarding the efficacy in patients with high body mass index (BMI). MATERIALS AND METHODS: All consecutive patients undergoing sentinel lymph node biopsies (SLNBs) for early breast cancer in NHS Tayside were included in a prospective audit of surgical and pathology findings. All patients included in the study received dual injection of patent blue dye and ICG. Approval was obtained from the local Caldicott guardian for collection and use of personal data. RESULTS: Of 239 cases, all were female patients of mean age 62 years (range 27-93). In 4.2% (10/239) of cases, neither blue dye nor ICG was present in the axilla. Of the remaining 229 SLNB cases in this series, surgeons documented retrieval of 451 nodes, with a mean surgical nodal count per case of 1.97 (range 1-5) and pathological nodal count of 2.15 (range 0-7). Eighty three cases were performed in patients with BMI 30-39.9 and 21 cases with BMI ≥40, with nodal detection rates of 96.4% (80/83) and 95.2% (20/21), respectively, in these groups of patients. Twenty percent (48/229) of cases had nodal metastases on histopathology. CONCLUSIONS: This is a large single-center study which demonstrates the safety and accuracy of the combined ICG and blue dye technique for SLNB in breast cancer. This is represented by nodal detection rates and node positivity rates which are comparable to previous multicenter studies of standard SLNB regardless of BMI.

Bilateral breast necrotizing leukocytoclastic vasculitis: First case report.

Leukocytoclastic vasculitis (LCV) is a very rare immune complex-mediated condition affecting the small vessels walls. We present the case of a 48-year-old woman with necrotizing bilateral breast LCV on treatment with glatiramer acetate for multiple sclerosis. Bilateral mastectomies and debridement of the anterior abdominal wall were required due to the rapidly evolving necrotizing process. Rapid assessment and a multidisciplinary approach are fundamental in treating this rare life-threatening condition.

The Impact of the COVID-19 Pandemic on Surgical Management of Breast Cancer: Global Trends and Future Perspectives.

INTRODUCTION: The rapid spread of COVID-19 across the globe is forcing surgical oncologists to change their daily practice. We sought to evaluate how breast surgeons are adapting their surgical activity to limit viral spread and spare hospital resources. METHODS: A panel of 12 breast surgeons from the most affected regions of the world convened a virtual meeting on April 7, 2020, to discuss the changes in their local surgical practice during the COVID-19 pandemic. Similarly, a Web-based poll based was created to evaluate changes in surgical practice among breast surgeons from several countries. RESULTS: The virtual meeting showed that distinct countries and regions were experiencing different phases of the pandemic. Surgical priority was given to patients with aggressive disease not candidate for primary systemic therapy, those with progressive disease under neoadjuvant systemic therapy, and patients who have finished neoadjuvant therapy. One hundred breast surgeons filled out the poll. The trend showed reductions in operating room schedules, indications for surgery, and consultations, with an increasingly restrictive approach to elective surgery with worsening of the pandemic. CONCLUSION: The COVID-19 emergency should not compromise treatment of a potentially lethal disease such as breast cancer. Our results reveal that physicians are instinctively reluctant to abandon conventional standards of care when possible. However, as the situation deteriorates, alternative strategies of de-escalation are being adopted. IMPLICATIONS FOR PRACTICE: This study aimed to characterize how the COVID-19 pandemic is affecting breast cancer surgery and which strategies are being adopted to cope with the situation.

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

Bariatric surgery attenuates colitis in an obese murine model.

BACKGROUND: Obesity and inflammatory bowel disease (IBD) represent chronic inflammatory conditions. Bariatric surgery improves some obesity-related co-morbidities, but the effects of bariatric surgery on IBD have not been well studied. OBJECTIVES: To examine if bariatric surgery may attenuate colitis in an obese murine model of IBD and study the mechanisms underlying the postsurgical amelioration of intestinal inflammation. SETTING: University of California Irvine, Department of Surgery and Microbiology laboratories. METHODS: Obese mice were assigned to one of 2 bariatric procedures [Duodenojejunal Bypass (DJB n = 6), Sleeve Gastrectomy (SG n = 8)]. Sham-operated mice were (Sham n = 8) were used as a control. After recovering from surgery, IBD was induced by administration of 2% dextran sodium sulfate. Fecal samples were collected before and after IBD induction for microbiome analysis. Pathologic analyses and immunohistochemical staining were performed on colon. RESULTS: Survival after DJB and SG was higher relative to Sham mice. Histologically, DJB mice had significantly less intestinal inflammation. The observed improvements were not related to a difference in weight among the groups. Farnesoid X receptor staining in the colon was observed quantitatively more in DJB than in SG and sham mice. A statistically significant increase in the number of Lactobacillales was observed in the stool of mice after DJB. CONCLUSION: These results suggest that bariatric surgery, in particular DJB, reduces the severity of colitis in a chemically-induced IBD murine model. The anticolitis effects of DJB may be associated with Farnesoid X receptor regulation and gut microbiome rearrangements.

Real-World Clinical Practice of Intensified Chemotherapies for Metastatic Pancreatic Cancer: Results from a Pan-European Questionnaire Study.

INTRODUCTION: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe. METHODS: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer. RESULTS: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer. CONCLUSION: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.

Future of Minimally Invasive Colorectal Surgery.

Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics.

Retrorectal Tumors: A Comprehensive Literature Review.

IMPORTANCE: Retrorectal tumors are rare lesions that comprise a multitude of histologic types. Reports are limited to small single-institution case series, and recommendations on the ideal surgical approaches are lacking. OBJECTIVE: The purpose of the study was to provide a comprehensive review of the epidemiology, pathologic subtypes, surgical approaches, and clinical outcomes of retrorectal tumors. EVIDENCE REVIEW: We conducted a review of the literature using PubMed and searched the reference lists of published studies. RESULTS: A total of 341 studies comprising 1708 patients were included. Overall, 68 % of patients were female. The mean age was 44.6 ± 13.7 years. Of all patients, 1194 (70 %) had benign lesions, and 514 patients (30 %) had malignant tumors. Congenital tumors (60.5 %) were the most frequent histologic type. Other pathologic types were neurogenic tumors (14.8 %), osseous tumors (3.1 %), inflammatory tumors (2.6 %), and miscellaneous tumors (19.1 %). Biopsy was performed in 27 % of the patients. Of these patients, incorrect diagnoses occurred in 44 %. An anterior surgical approach (AA) was performed in 299 patients (35 %); a posterior approach (PA) was performed in 443 (52 %), and a combined approach (CA) was performed in 119 patients (14 %). The mean length of stay (LOS) of PA was 7 ± 5 days compared to 8 ± 7 days for AA and 11 ± 7 days for CA (p < 0.05). The overall morbidity rate was 13.2 %: 19.3 % associated with anterior approach, 7.2 % associated with posterior approach, and 24.7 % after a combined approach (p < 0.05). Overall postoperative recurrence rate was 21.6 %; 6.7 % after an anterior approach, 26.6 % after a posterior approach, and 28.6 % after a combined approach (p < 0.05). A minimally invasive approach (MIS) was employed in 83 patients. MIS provided shorter hospital stays than open surgery (4 ± 2 vs. 9 ± 7 days; p < 0.05). Differences in complication rate were 19.8 % in MIS and 12.2 % in open surgery and not statistically significant. CONCLUSIONS AND RELEVANCE: Retrorectal tumors are most commonly benign in etiology, of a congenital nature, and have a female predominance. Complete surgical resection is the cornerstone of retrorectal tumor management. A minimal access surgery approach, when feasible, appears to be a safe option for the management of retrorectal tumors, with shorter operative time and length of stay.

Prognostic and predictive markers in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant.

From CT scanning to 3-D printing technology for the preoperative planning in laparoscopic splenectomy.

BACKGROUND: Three-dimensional printing technology is rapidly changing the way we produce all sort of objects, having also included medical applications. We embarked in a pilot study to assess the value of patient-specific 3-D physical manufacturing of spleno-pancreatic anatomy in helping during patient's counseling and for preoperative planning. METHODS: Twelve patients scheduled for a laparoscopic splenectomy underwent contrast CT and subsequent post-processing to create virtual 3-D models of the target anatomy, and 3-D printing of the relative solid objects. The printing process, its cost and encountered problems were monitored and recorded. Patients were asked to rate the value of 3-D objects on a 1-5 scale in facilitating their understanding of the proposed procedure. Also 10 surgical residents were required to evaluate the perceived extra value of 3-D printing in the preoperative planning process. RESULTS: The post-processing analysis required an average of 2; 20 h was needed to physically print each model and 4 additional hours to finalize each object. The cost for the material employed for each object was around 300 euros. Ten patients gave a score of 5, two a score of 4. Six residents gave a score of 5, four a score of 4. CONCLUSIONS: Three-dimensional printing is helpful in understanding complex anatomy for educational purposes at all levels. Cost and working time to produce good quality objects are still considerable.

Short-term outcomes of single-site robotic cholecystectomy versus four-port laparoscopic cholecystectomy: a prospective, randomized, double-blind trial.

BACKGROUND: Randomized studies could not demonstrate significant outcome benefit after single-incision laparoscopic cholecystectomy compared to classic four-port laparoscopic cholecystectomy (CLC). The new robotic single-site platform might offer potential benefits on local inflammation and postoperative pain due to its technological advantages. This prospective randomized double-blind trial compared the short-term outcomes between single-incision robotic cholecystectomy (SIRC) and CLC. METHODS: Two groups of 30 eligible patients were randomized for SIRC or CLC. During the first postoperative week, patients and study monitors were blinded to the type of procedure performed by four dressing tapes applied on the abdomen. Pain was assessed at 6 h and on day 1, 7 and 30 after surgery, along with a 1-10 cosmetic score. RESULTS: No significant difference in postoperative pain occurred in the two groups at any time point nor for any of the abdominal sites. Nineteen (63 %) SIRC patients reported early postoperative pain in extra-umbilical sites. Intraoperative complications which might influence postoperative pain, such as minor bleeding and bile spillage, were similar in both groups and no conversions occurred. The cosmetic score 1 month postoperatively was higher for SIRC (p < 0.001). Two SIRC patients had wound infection, one of which developed an incisional hernia. CONCLUSIONS: SIRC does not offer any significant reduction of postoperative pain compared to CLC. SIRC patients unaware of their type of operation still report pain in extra-umbilical sites like after CLC. The cosmetic advantage of SIRC should be balanced against an increased risk of incisional hernias and higher costs. TRIAL REGISTRATION NUMBER: ACTRN12614000119695 ( http://www.anzctr.org.au ).

New Advances in the Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extremely poor overall survival (OS) compared to other solid tumours. As the incidence of the disease is rising and the treatment options are limited, PDAC is projected to be the 2nd leading cause of cancer-related deaths in the United States by 2030. A majority of patients are not eligible for curative resection at the time of diagnosis, and those that are resected will often relapse within the first few years after surgery. SUMMARY: Until recently, the nucleoside analogue gemcitabine has been the standard of care for patients with non-resectable PDAC with only marginal effects on OS. In 2011, the gemcitabine-free FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) showed a significant survival advantage for patients with metastatic PDAC in a phase III trial. In 2013, the Metastatic Pancreatic Adenocarcinoma Trial phase III trial with nano- formulated albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine also resulted in a significant survival extension compared to gemcitabine monotherapy. However, both intensified therapy regimens show a broad spectrum of side effects and patients need to be carefully selected for the most appropriate protocol. KEY MESSAGE: In this study, recent advances in the chemotherapeutic options available to treat metastatic PDAC and their implications for today's treatment choices are reviewed.

Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma.

We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

Diverting ileostomy in colorectal surgery: when is it necessary?

PURPOSE: The role of fecal diversion using a loop ileostomy in patients undergoing rectal resection and anastomosis is controversial. There has been conflicting evidence on the perceived benefit vs. the morbidity of a defunctioning stoma. This is a review of the relevant surgical literature evaluating the risks, benefits, and costs of constructing a diverting ileostomy in current colorectal surgical practice. METHODS: Retrospective and prospective articles spanning the past 50 years were reviewed to identify the definition of an anastomotic leak (AL), evaluate risk factors for AL, and assess methods of evaluation of the anastomosis. We then pooled the evidence for and against fecal diversion, the incidence and consequences of stomal complications, and the evidence comparing loop ileostomy vs. loop colostomy as the optimal method of fecal diversion. RESULTS: Evidence shows that despite the fact that fecal diversion does not decrease postoperative mortality, it does significantly decrease the risk of anastomotic leak and the need for urgent reoperation when a leak does occur. Diverting stomas are a low-risk surgical procedure from a technical standpoint but carry substantial postoperative morbidity that can greatly hamper patients' quality of life and recovery. High-risk patients such as those with low colorectal anastomoses (<10 cm from anal verge), colo-anal anastomoses, technically difficult resections, malnutrition, and male patients seem to reap the greatest benefit from fecal diversion. CONCLUSIONS: Fecal diversion is recommended as a selective tool to protect or ameliorate an anastomotic leak after a colorectal anastomosis. It is most beneficial when used selectively in high-risk patients with low pelvic anastomoses that are at an increased risk for AL. New tools are needed to identify patients at high risk for anastomotic failure after anterior resection.

Overcoming the challenges of single-incision cholecystectomy with robotic single-site technology.

OBJECTIVE: To analyze the preliminary experience with the new da Vinci single-site technology for cholecystectomy. HYPOTHESIS: Single-incision laparoscopic cholecystectomy is technically challenging and a related learning curve clearly exists. A novel approved robotic single-port platform has recently been introduced. This technology may help overcome some of the limitations of manual single-incision surgery relating to triangulation of instruments, ergonomics, and surgical exposure. DESIGN: A prospective longitudinal observational study was conducted on 100 consecutive da Vinci single-site cholecystectomies. SETTING: Five Italian centers of robotic general surgery. MAIN OUTCOME MEASURES: Primary end points were feasibility without conversion and the absence of major complications. Operative times were analyzed to define the learning curve using a mixed regression model.A questionnaire collected the opinions of the surgeons involved in using the new technique. RESULTS: Two patients underwent conversion. No major intraoperative complications occurred, but there were 12 minor incidents (7 ruptures of the gallbladder and 5 cases of minor bleeding from the gallbladder bed). Mean (SD) total operative time was 71 (19) minutes, with a mean (SD) console time of 32 (13) minutes. No significant reduction in the operative times was observed with the increasing of each surgeon's experience. The technique was judged more complex than standard 4-port laparoscopy but easier than single-incision laparoscopy. CONCLUSIONS: Da Vinci single-site cholecystectomy is an easy and safe procedure for expert robotic surgeons. It allows the quick overcoming of the learning curve typical of single-incision laparoscopic surgery and may potentially increase the safety of this approach.

Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation.

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation.