Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

BACKGROUND: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. STUDY DESIGN: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. RESULTS: A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). CONCLUSION: RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.

Laparoscopic Compared with Open D2 Gastrectomy on Perioperative and Long-Term, Stage-Stratified Oncological Outcomes for Gastric Cancer: A Propensity Score-Matched Analysis of the IMIGASTRIC Database.

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS: Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Malignant triton tumor below the peritoneal reflection: a case report.

Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumors (MPNSTs) histologically defined by rhabdomyoblastic differentiation. MTTs are primarily found in the head, neck, extremities and trunk, but rare cases of MTT within the buttock, the mediastinum and the retroperitoneum have also been documented. We present the case of a 47-year-old male patient who initially presented with right flank pain and hematuria in July 2019, who was found to have a large pelvic mass below peritoneal reflection. Complete resection of the mass was performed, and pathology identified the mass as a MTT.

Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery.

AIM: To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes. METHODS: This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided. RESULTS: The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery (P = 0.42) and stage of the disease (P = 0.16). Intraoperative blood loss was significantly lower in the LG (95.93 ± 119.22) and RG (117.91 ± 68.11) groups compared to the OG (127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG (27.78 ± 11.45), LG (24.58 ± 13.56) and OG (25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay (P < 0.0001). A similar complications rate was found (P = 0.13). The leakage rate was not different (P = 0.78) between groups. CONCLUSION: Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines.

Pancreatic adenocarcinoma is one of the most deadly malignancies, and endometrial cancer represents the most common gynecologic cancer in the USA. Better understanding on the pathologic mechanisms and pathways is required for effective treatment of these malignancies. Recently, human epididymis protein 4 (HE4 or WFDC2), a secretory glycoprotein, was found to be overexpressed in pancreatic and endometrial cancers. In addition, studies have shown that HE4 overexpression in endometrial cancer cell lines led to faster cancer progression in a mouse subcutaneous model. These findings raise a question on the role(s) of secretory, extracellular HE4 in cancer development. In the present study, we found that treatment of pancreatic and endometrial cancer cell lines with purified, extracellular HE4 protein led to a significant increase in cell viability and proliferation. Moreover, extracellular HE4 protein was able to increase DNA synthesis, and modulate the mRNA and protein levels of cell cycle marker PCNA and cell cycle inhibitor p21. These effects appeared to be robust and sustainable and required a relatively low concentration of HE4 protein. The findings indicated the secreted, extracellular HE4 may carry some physiopathological functions. Via paracrine/endocrine actions, circulatory HE4 produced by malignant cells may contribute to pancreatic and endometrial cancer progression and/or metastasis.

Robotic, laparoscopic and open surgery for gastric cancer compared on surgical, clinical and oncological outcomes: a multi-institutional chart review. A study protocol of the International study group on Minimally Invasive surgery for GASTRIc Cancer-IMIGASTRIC.

INTRODUCTION: Gastric cancer represents a great challenge for healthcare providers and requires a multidisciplinary treatment approach in which surgery plays a major role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and recently with the spread of robotic surgery, but a number of issues are currently being debated, including the limitations in performing an effective extended lymph node dissection, the real advantages of robotic systems, the role of laparoscopy for Advanced Gastric Cancer, the reproducibility of a total intracorporeal technique and the oncological results achievable during long-term follow-up. METHODS AND ANALYSIS: A multi-institutional international database will be established to evaluate the role of robotic, laparoscopic and open approaches in gastric cancer, comprising of information regarding surgical, clinical and oncological features. A chart review will be conducted to enter data of participants with gastric cancer, previously treated at the participating institutions. The database is the first of its kind, through an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centres. ETHICS AND DISSEMINATION: This study is conducted in compliance with ethical principles originating from the Helsinki Declaration, within the guidelines of Good Clinical Practice and relevant laws/regulations. A multicentre study with a large number of patients will permit further investigation of the safety and efficacy as well as the long-term outcomes of robotic, laparoscopic and open approaches for the management of gastric cancer. TRIAL REGISTRATION NUMBER: NCT02325453; Pre-results.

Promoter Hypermethylation and Decreased Expression of Syncytin-1 in Pancreatic Adenocarcinomas.

Syncytin-1 is a member of human endogenous retroviral W gene family (HERVW1). Known to be expressed in human placental trophoblast, syncytin-1 protein mediates the fusion of cytotrophoblasts for the formation of syncytiotrophoblasts, the terminally differentiated form of trophoblast lineage. In addition, in vitro studies indicate that syncytin-1 possessed nonfusogenic functions such as those for immune suppression, cell cycle regulation and anti-apoptotic activities. Overexpression of syncytin-1 has been observed in various malignant tissues including breast, endometrial and ovarian cancers. It was reported that syncytin-1 gene expression is associated with dynamic changes of DNA hypomethylation in the 5' LTR. In this study, applying the real-time PCR, Western blot analysis and immunohistochemistry methods, we demonstrate a constitutive expression of syncytin-1 in normal pancreas tissues as well as normal tissues adjacent to cancer lesions. Moreover, a reduced expression is found in the pancreatic adenocarcinoma tissues. The expression levels of syncytin-1 are not correlated with the stage, historical grade and gender, but inversely correlated with patients' age. Furthermore, COBRA and bisulfite sequencing results indicated that the lower expression of syncytin-1 is correlated with the hypermethylation of two CpG dinucleotides in the 5' LTR of syncytin-1 gene. The nonfusogenic function of syncytin-1 in normal pancreas as well as its role(s) in the pathogenesis and progression of pancreatic cancers remains to be investigated. Identification of the two CpG dinucleotides around transcription start site as key epigenetic elements has provided valuable information for further studies on the epigenetic regulation of syncytin-1 in pancreatic cancer cells.

Current status of minimally invasive surgery for gastric cancer: A literature review to highlight studies limits.

BACKGROUND: Gastric cancer represents a great challenge for health care providers and requires a multidisciplinary approach in which surgery plays the main role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and more recently with the spread of robotic surgery, but a number of issues are currently being investigate, including the limitations in performing effective extended lymph node dissections and, in this context, the real advantages of using robotic systems, the possible role for advanced Gastric Cancer, the reproducibility of completely intracorporeal techniques and the oncological results achievable during follow-up. METHOD: Searches of MEDLINE, Embase and Cochrane Central Register of Controlled Trials were performed to identify articles published until April 2014 which reported outcomes of surgical treatment for gastric cancer and that used minimally invasive surgical technology. Articles that deal with endoscopic technology were excluded. RESULTS: A total of 362 articles were evaluated. After the review process, data in 115 articles were analyzed. CONCLUSION: A multicenter study with a large number of patients is now needed to further investigate the safety and efficacy as well as long-term outcomes of robotic surgery, traditional laparoscopy and the open approach.

Expression and diagnostic value of HE4 in pancreatic adenocarcinoma.

Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma.

Race/Ethnicity is predictive of lymph node status in patients with early gastric cancer.

BACKGROUND: Race/ethnicity has long been suspected to affect survival in patients with gastric adenocarcinoma. However, the clinicohistopathological impact of race or ethnicity on early gastric cancer (EGC) is not known. METHODS: From 2000 to 2013, 286 patients underwent gastrectomy and 104 patients had pathological confirmation of EGC. A retrospective analysis of pathological and clinical prognostic indicators was performed. RESULTS: The study population consisted of 38 (37%) Asian Americans and 66 (63%) non-Asian Americans. Of these, 2 (5.3%) Asian Americans and 19 (28.8%) non-Asian Americans had pathological confirmation of lymph node metastasis (LNM) (p = 0.004). Univariate analysis comparing the clinicohistopathological characteristics in each group did not reveal significant difference regarding histotype, tumor size, grade, location, morphology, or lymphovascular invasion, except for the LNM rate and mean body mass index (23.2 versus 26.6, p < 0.001). Multivariate analysis showed that non-Asian race/ethnicity (odds ratio (OR), 9.09; 95% confidence interval (CI), 1.12-71.43; p = 0.038), younger age (OR, 1.11; 95% CI, 1.01-1.12; p = 0.046), and lymphovascular invasion (OR, 13.9; 95% CI, 2.40-79.99; p = 0.003) were significant predictors for LNM. CONCLUSIONS: This study demonstrated that Asian American race in EGC is associated with a significantly decreased rate of LNM in comparison to non-Asian Americans, despite similar histopathological characteristics of each group.

Evidence-based review of the management of early gastric cancer.

Although standard gastrectomy remains the most definitive locoregional treatment for early gastric cancer, it carries significant perioperative morbidities. Surgical gastrectomy for resection of lymph nodes is not always required and endoscopic resection may be a treatment option for patients at negligible risk of lymph node metastasis. Furthermore, the criteria for endoscopic resection are expanding, along with the development of new technology, in both Eastern and western countries with high prevalence of early gastric cancer, where studies for endoscopic treatment modalities have been conducted. Within such a trend, however, it should be emphasized that early gastric cancer needs to be treated cautiously, especially in western countries, as several studies suggest that there may be differences in tumor biology and aggressiveness between Asian and non-Asian populations.

Standardization of surgical and pathologic variables is needed in multicenter trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031 trial.

BACKGROUND: Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC). METHODS: To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome. RESULTS: 80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria. CONCLUSIONS: Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.

Minimally invasive surgery and cancer: controversies part 1.

Perhaps there is no more important issue in the care of surgical patients than the appropriate use of minimally invasive surgery (MIS) for patients with cancer. Important advances in surgical technique have an impact on early perioperative morbidity, length of hospital stay, pain management, and quality of life issues, as clearly proved with MIS. However, for oncology patients, historically, the most important clinical questions have been answered in the context of prospective randomized trials. Important considerations for MIS and cancer have been addressed, such as what are the important immunologic consequences of MIS versus open surgery and what is the role of laparoscopy in the staging of gastrointestinal cancers? This review article discusses many of the key controversies in the minimally invasive treatment of cancer using the pro-con debate format.

Retroperitoneal foregut duplication cyst presenting as an adrenal mass.

A 75 year-old woman presented to the authors' institution with abdominal pain and early satiety. An adrenal mass was found on CT scanning. Laparoscopic adrenalectomy was performed, and the patient was found to have a retroperitoneal bronchogenic cyst adherent to the adrenal gland. The workup of an adrenal mass is discussed as well as the pathophysiology of bronchogenic cysts.

Minimally invasive esophagectomy: early experience and outcomes.

Minimally invasive esophageal surgery has the potential to improve mortality, hospital stay, and functional outcomes when compared with open methods. Although technically complex, combined laparoscopic and thoracoscopic esophageal resection is feasible. A case series of 20 patients who underwent minimally invasive total esophagectomy is presented. This study was a review of a prospective database. The purpose was to evaluate early results with laparoscopic total esophagectomy for benign and malignant disease. Between January 2003 and November 2005, 20 patients underwent minimally invasive esophageal surgery. All operations were performed by the same two surgeons. Age, gender, indications for surgery, pathologic stage, operative time, blood loss, transfusion requirements, intensive care unit length of stay, hospital length of stay, postoperative complications, and mortality were recorded. Diet progression, dysphagia, and need for stricture management were also recorded. Of the 20 minimally invasive total esophagectomies performed, 18 (90%) were completed successfully. The average age of the patients was 53 years. Indications for surgery were malignancy (n = 13), carcinoma in situ in the setting of Barrett's esophagus (n = 2), and benign stricture (n = 3). The average operating time was 467 minutes (range 346-580 min). Median blood loss was 350 mL (range 150-500 mL). The median intensive care unit stay was 2 days, and the median hospital length of stay was 12 days. Pathology revealed that 7 per cent of patients had stage I disease, 27 per cent of patients had stage II disease, and 53 per cent of patients had stage III disease. There was a single mortality (5%), a cervical leak in two patients (10%), a gastric tip necrosis in one patient (5%), and tracheoesophageal fistula in one patient (5%). Major complications occurred in eight patients (40%) and minor complications in nine (50%). Thirteen (72%) patients were discharged on enteral tube feeds to supplement caloric intake. The application of minimally invasive techniques in the arena of esophageal surgery continues to evolve. This approach has the potential to improve mortality, hospital stay, and other outcomes when compared with open methods. Although technically complex, laparoscopic total esophagectomy is feasible.