Patients Underwent R0 Resection Research Articles

Synchronous colorectal and liver resections: Safety and efficacy of the Colon-Liver-Colon operative sequence.

Background: Surgical management of patients with colorectal cancer (CRC) and synchronous liver metastases (CRLM) has evolved significantly during the past decades. An increasing number of studies have demonstrated encouraging Results in selected patients undergoing synchronous resections (SR) of the primary CRC and CRLM. The aim of our study was to evaluate the safety and efficacy of our Colon-Liver-Colon (COLICO) operative sequence approach in patients undergoing synchronous resections. Materials and Methods: Outcomes of patients who underwent SR of primary CRC and CRLM at our institution from by one certified HPB surgeon during a 4-year period were retrospectively evaluated. During the COLICO operative sequence, the CRC resection was initially performed without creation of anastomosis, followed by LM resection and finally creation of the bowel anastomosis in the absence of factors, which could postoperatively compromise its integrity. Results: A total of 15 patients (6 men) underwent SR of CRC and CRLM. Right colectomy, sigmoidectomy and low anterior resection were performed in 6, 5 and 4 patients, respectively. All patients underwent minor liver resection. The median number of LM resected was 3 (range 1-8). Five patients underwent additional radiofrequency ablation of LM. Diverting ileostomy was performed in only 1 patient. All patients underwent R0 resection of both CRC and CRLM. No anastomotic leaks were documented. Overall morbidity and 90-day mortality were 20% and 0%, respectively. The 1- and 3-year overall survival of patients was 93% and 66%, respectively. Conclusions: According to our outcomes, the COLICO approach seems a safe and efficient approach for selected patients with resectable synchronous LMs. Selection of patients is of cardinal importance for the performance of SR. Intraoperative parameters such as increased blood loss and prolonged operative time must be taken under account for the performance of the colic anastomosis in order to reduce potential postoperative morbidity and mortality.

Surgical Management of Gastric Cancer: An Institutional Experience

Introduction: Gastric cancer (GC) is the second most common cause of cancer-related deaths causing about 800,000 deaths worldwide/year. In Nepal gastric cancer is the second common cancer among males after the lung cancer. Gastric cancer shows a wide variation in incidence worldwide, being highest in Korea and Japan. It is detected early due to the low threshold for upper gastrointestinal endoscopy and screening programs. In the rest of the world and particularly in developing countries, GC is advanced in most of the cases. Inspite of controversies in extent of resection and lymphadenectomy, surgery remains the gold standard treatment. The study was conducted to determine the outcome of the patients with gastric cancer.
 Methods: The study was conducted in the department of surgery at Nepalgunj Medical College and Teaching Hospital Kohalpur from November 2015 to Dec 2018. Patients diagnosed with GC were studied. The patients with resectable disease underwent radical resection followed by adjuvant chemo-radiation as indicated. Patient’s demography, clinical presentation, stage of disease, types of surgery performed and survival were analysed.
 Results: 58 patients were diagnosed with gastric cancer. The age ranged from 20-83 years with the mean of 61.26±11.28. Male to female ratio was 2.41: 1. The common clinical presentations were weight loss, anorexia and anemia, 17 (29.31%) had gastric outlet obstruction at initial presentation and 4 (6.89%) presented with perforation peritonitis. Antropyloric region was the commonest site of tumor location seen in 41 (70.68%). 7 (12.06%) patients had distant metastasis and 5 (8.62%) had ascites at presentation. Out of 58 patients, 43 (74.13%) were operated. Only 18 (41.86%) patients underwent R0 resection. 14 (24.13%) underwent palliative gastrojejunostomy. Two (3.44%) patients underwent primary repair for perforation and in 9 (15.51%) the procedure was abandoned due to and presence of metastasis. There was one post-operative mortality. The histology of gastric cancer was found to be adenocarcinoma in all patients. There was no patient in stage I. 3(16.66%) patients were in stage II and 15 (83.33%) in stage III. 17 (29.31%) had stage IV disease. Out of 43 operated patients, 13 lost follow up. All 17 resected patients and those with metastatic disease were followed up. There was no death and no local recurrence in stage II. In stage III, 78.57% were alive and in stage IV 35.29% were alive.
 Conclusion: Gastric cancer is one of the common gastrointestinal malignancies affecting predominantly male gender. Stage of the disease is one of the major prognostic factors related with the survival. Adenocarcinoma is the commonest histology. Radical resection followed by adjuvant chemotherapy is the standard of care. Palliative chemotherapy can prolong the overall survival in patients with metastatic disease.

Who benefits from R0 resection? A single-center analysis of patients with stage Ⅳ gallbladder cancer

ObjectivesMost patients with gallbladder cancer (GBC) present with advanced-stage disease and have a poor prognosis. Radical resection remains the only therapeutic option to improve survival in patients with GBC. This study aimed to analyze the prognostic factors in patients with stage Ⅳ GBC and to identify a subgroup of patients who might benefit from R0 resection. MethodsA total of 285 patients with stage Ⅳ GBC were retrospectively analyzed at our institution from January 2008 to December 2012. Factors potentially influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analyses. ResultsThe 1-, 3-, and 5-year overall survival rates were 6.6% (15/229), 0.9% (2/229), and 0 (0/229), respectively. Ascites (relative risk [RR] = 1.631, 95% confidence interval [CI]: 1.221–2.180, P = 0.001), pathological grade (RR = 1.337, 95% CI: 1.050–1.702, P = 0.018), T stage (RR = 1.421, 95% CI: 1.099–1.837, P = 0.000), M stage (RR = 1.896, 95% CI: 1.409–2.552, P = 0.000), and surgery (RR = 1.542, 95% CI: 1.022–2.327, P = 0.039) were identified as independent risk factors influencing prognosis. The median survival time (MST) was significantly higher in patients undergoing R0 resection than in those undergoing R1/R2 resection (6.0 vs. 2.7 months; P < 0.001). In subgroup analyses, stage ⅣA patients benefited from R0 resection (MST for R0 vs. R1/R2, 11.0 vs. 4.0 months; P = 0.003), while R0 resection had a significant survival benefit than R1/R2 resection in patient with stage ⅣB GBC without distant metastasis (MST for R0 vs. R1/R2, 6.0 vs. 3.0 months; P = 0.007). ConclusionAscites, pathological grade, T stage, M stage, and surgery were independent risk factors influencing prognosis in patients with stage IV GBC. N2 lymph node metastasis did not preclude curative resection, and radical resection should be considered in patients with stage Ⅳ GBC without distant metastasis once R0 margin was achieved.

Dose escalated concurrent chemo-radiation in borderline resectable and locally advanced pancreatic cancers with tomotherapy based intensity modulated radiotherapy: a phase II study.

We report the response and outcomes of borderline resectable and locally advanced pancreatic cancer (BRPC & LAPC) patients treated with dose escalated neoadjuvant intensity modulated radiotherapy (IMRT). Thirty newly diagnosed patients with BRPC (n=18) and LAPC (n=12) (NCCN criteria V 2.2.12) were accrued in this prospective study from 2008-2011. All patients received neoadjuvant chemoradiation (NACRT) using Helical Tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor volume (GTV) and 45 Gy over 25 fractions to suspected microscopic extension) along with weekly gemcitabine. Fifteen patients (50%) had a partial response. A complete metabolic response (CMR) on PET was seen in 9 patients (30%). Among BRPC, 9 patients (50%) were surgically explored and 7 underwent R0 resection (39%). The median follow up of surviving patients was 85 [interquartile range (IQR): 64.5-85.8] months. The median progression free survival (PFS) was 13 months for BRPC and 8.8 months for LAPC. The median overall survival (OS) was 17.3 months for BRPC and 11.8 months for LAPC. Among patients undergoing R0 resection, the median PFS and OS was 27 and 35.5 months respectively. Dose escalated radiotherapy with concurrent chemotherapy is feasible and can downsize some tumors resulting in surgery in about 39% of the BRPC.

Elevated Controlling Nutritional Status (CONUT) Score is Associated with Poor Long-term Survival in Patients with Low-grade Soft-tissue Sarcomas Treated with Surgical Resection.

Several studies have examined the Controlling Nutritional Status (CONUT) score, which is a screening tool for nutritional status and an effective biomarker for patient survival after cancer treatment. However, its role in soft-tissue sarcoma (STS) remains unknown. Because of the lack of predictive markers for survival in patients with STS, we aimed to determine the CONUT score's association with survival. (1) Is there a relationship between the CONUT score and clinicopathologic characteristics such as tumor size, tumor location, pathological grade, and advanced stage based on the American Joint Committee on Cancer (AJCC) guidelines? (2) Is the CONUT score associated with disease-free survival (DFS) and overall survival (OS) in patients treated surgically for STS, even when compared with other systemic inflammatory response markers? Between 1999 and 2016, 769 patients underwent R0 resection for STS at our institution. Adequate medical records and available followup data were required for inclusion in this study. Exclusion criteria were synchronous inflammatory diseases, unplanned excision, and neoadjuvant therapy. There were 658 patients (86%) who fulfilled all criteria. The minimum followup time was 24 months (median, 103 months; range, 61-147 months). The median age of the patients was 43 years (range, 5-85 years), and 265 patients (40%) were women. All patients had Stage I to IV tumors according to the 8 edition of the AJCC staging system. The grade classification was determined to be G1 in 130 patients (20%), G2 in 304 (46%), and G3 in 201 (31%). The CONUT score was calculated based on the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. The score ranged from 0 to 12, with higher scores indicating worse nutritional status. The patients were classified into two groups according to a receiver operating characteristic curve analysis: the high (≥ 2) and low (0 or 1) CONUT score groups. There were 435 patients in the low CONUT score group and 223 in the high CONUT score group. We tested for an association between the CONUT scores and gender, age, tumor diameter, tumor depth, tumor grade, and AJCC stage using the chi-square and Fisher's exact methods. We also compared the strength of the association between postoperative survival and the CONUT scores, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) using multivariate Cox proportional hazard model analyses. High CONUT scores were associated with large tumor size (odds ratio [OR], 1.47; 95% CI, 1.06-2.04; p = 0.020), deep tumor location (OR, 1.66; 95% CI, 1.17-2.36; p = 0.004), high tumor grade (OR, 2.54; 95% CI, 1.56-4.14; p = 0.001), and advanced AJCC stage (OR, 1.86; 95% CI, 1.14-3.02; p < 0.001). The low CONUT score group exhibited a higher 5-year OS rate and longer OS than the high CONUT score group (82% versus 65%; odds ratio, 2.45; 95% CI, 1.27-4.72; p < 0.001; 81 versus 64 months, Z = -2.56; p < 0.001). A multivariate analysis indicated that an elevated CONUT score was an independent predictor of OS (hazard ratio [HR], 1.86; 95% CI, 1.47-4.14; p < 0.001) and DFS (HR, 1.63; 95% CI, 1.26-2.11; p < 0.001), but the NLR and PLR were not. In an individual subgroup analysis, the CONUT scores were associated with OS and DFS in the tumor diameter (< 5 or ≥ 5 cm) subgroup, tumor depth (superficial or deep) subgroup, tumor grade (G1 and G2) subgroup, and AJCC stage (I/II or III/IV) subgroup, but not in the G3 subgroup (p = 0.051 and p = 0.065). High CONUT scores were independently associated with aggressive tumor behavior and unfavorable survival for patients with low-grade, but not high-grade, resected STS. If these findings can be substantiated in larger studies, the CONUT score might be useful for predicting survival and help to develop new treatment strategies for nutrition interventions. Level III, therapeutic study.

Long-term postresection prognosis of primary neuroendocrine tumors of the liver.

PurposePrimary hepatic neuroendocrine tumor (PHNET) is a very rare neoplasm, requiring strict exclusion of metastasis from possible extrahepatic primary sites for its diagnosis.MethodsWe reviewed our clinical experience of 13 patients with primary hepatic NET who underwent liver resection from January 1997 to December 2015.ResultsThe mean age of the 13 patients (8 males and 5 females) was 51.1 ± 12.8 years; the most common clinical manifestation was vague, nonspecific abdominal pain (n = 9). Of them, 11 patients underwent preoperative liver biopsy, 7 of which correctly diagnosed as neuroendocrine tumor (NET). Ten patients underwent R0 resection, and 3 underwent R1 resection. Diagnosis of PHNET was confirmed both immunohistochemically and by absence of extrahepatic primary sites. All tumors were single lesions, with a mean size of 9.6 ± 7.6 cm and a median size of 4.3 cm; all showed positive staining for synaptophysin and chromogranin. During a mean follow-up period of 95.1 ± 86.6 months, 7 patients died from tumor recurrence, whereas the other 6 remain alive to date, making the 5-year tumor recurrence rate 56.0% and the 5-year patient survival rate 61.5%. When confined to R0 resection, 5-year recurrence and survival rates were 42.9% and 70.0%, respectively. Univariate analysis showed that Ki-67 proliferative index was the only risk factor for tumor recurrence.ConclusionPHNET is a very rare tumor with no specific clinical features, and its final diagnosis depends primarily on pathology, immunohistochemistry, and exclusion of metastasis from other sites. Aggressive surgical treatment is highly recommended for PHNET because of acceptably favorable postresection outcomes.

Application of overlapped delta-shaped anastomosis technique in totally laparoscopic right hemicolectomy

To explore the safety and feasibility of the overlapped delta-shaped anastomosis (ODA) technique for cases undergoing totally laparoscopic right hemicolectomy (TLRH). Clinical data of patients who underwent TLRH using the ODA technique or the modified delta-shaped anastomosis (MDA) technique at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2016 to December 2017 were retrospectively analyzed. (1)diagnosed with adenocarcinoma by enteroscopy before operation; (2)cancer locating at ascending colon or transverse colon hepatic region and receiving TLRH surgery. (1) double or multiple primary colorectal cancers;(2)with complete or incomplete intestinal obstruction; (3) combined multiple organs resection; and (4) with unresectable distant metastases. The ileum and the transverse colon were sutured in an overlapped fashion about 8 cm away from the end of the ileum firstly, and then two small openings locating at the end of ileum and the corresponding site of the transverse colon were created in the ODA procedure, and the two small openings both locating at the end of ileum and the transverse colon were created in the MDA procedure. Statistical analysis was performed using SPSS 24.0 software and the general information, surgical and pathological results, and complications between two groups were compared. A total of 108 patients were enrolled in this study, including 52 patients in the ODA group and 56 patients in the MDA group. In the ODA group, 28 patients were male and 24 were female with age of (53.3±10.0) years and body mass index (BMI) of (24.2±2.7) kg/m2. In the MDA group, 27 patients were male and 29 were female with a mean age of (54.5±9.4) years and body mass index of (23.8±2.4) kg/m2. There were no significant differences between the two groups in terms of age, gender, BMI, history of previous abdominal surgery, scoring of American Society of Anesthesiologists, tumor location, pathological TNM stage, and number of dissected lymph node (all P>0.05). All the patients underwent R0 resection without conversion to open surgery or to extraperitoneal anastomosis. The time of anastomosis in the ODA group was shorter than that in the MDA group[(15.7±2.3) minutes vs.(18.6±3.6) minutes], and the difference was statistically significant (t=-5.017, P<0.001). There were no significant differences between two groups in total operative time[(160.7±17.8) minutes vs.(163.2±17.6) minutes], intraoperative blood loss [(77.7±28.3) ml vs.(75.9±31.8) ml], length of incision [(5.8±1.1) cm vs. (5.9±1.1) cm], time to first flatus [(1.8±0.2) days vs. (1.9±0.3) days], time to first oral intake [(1.9±0.5) days vs. (1.9±0.4) days], postoperative complications [3.8%(2/52) vs. 5.4%(3/56)], and postoperative hospital stay [(6.7±0.9) days vs. (6.8±0.8) days]. The ODA technique is less time-consuming without increasing postoperative complications compared to the MDA technique, which is a safe and feasible technique in TLRH worth further promotion.

Long-term results of robotic anatomical segmentectomy for early-stage non-small-cell lung cancer

Anatomical segmentectomy is advocated for curative resection in select patients. We investigated the long-term results of robotic anatomical segmentectomy with mediastinal nodal dissection in patients with early-stage lung cancer. We retrospectively reviewed patients who underwent robotic anatomical segmentectomy for early-stage non-small-cell lung cancer (NSCLC). The follow-up data were obtained to determine survival and statistically significant risk factors in both univariable and multivariable models. Seventy-one patients had clinical stage I NSCLC (36 men, 35 women, mean age 70 ± 12 years). All patients underwent R0 resection. The mean operating time was 134 min. Ten of 71 (14%) patients were upstaged. Eight of 71 (11%) patients were upstaged due to the size of tumour in the pathological specimen, and 2 of 71 (3%) patients were upstaged due to microscopic N2 nodal metastasis. Median hospitalization was 4 days (2-31 days). Complication rate was 29%. There were no complications attributable to the surgical robot. No patient died within 90 days. Mean follow-up was 54 months (range 2 months to 9 years). The overall 5-year survival was 43%, whereas lung cancer-specific 5-year survival was 55%. The 5-year lung cancer-specific survival for pathological stage I disease was 73%. Local or mediastinal recurrence occurred in 4 of 71(5%) patients. Pathological upstaging or recurrence resulted in 0% 5-year survival. The univariable and multivariable analyses showed that advanced age and pathological upstaging were statistically significant risk factors for lung cancer-specific death. Robotic anatomical segmentectomy with mediastinal nodal dissection is a safe and feasible procedure. Accurate preoperative clinical staging is of critical importance for long-term survival.

Outcomes associated with robotic approach to pancreatic resections.

Minimally invasive techniques have improved post-operative outcomes, however, the majority of pancreatic surgery, known for its complexity, is still performed via open approaches. The development of robotics has improved dexterity which may allow for application in more complex surgeries. We queried a prospectively maintained robotic database to identify patients who underwent robotic pancreatic resection by a single surgeon between 2012 and 2016. Patient demographics and operative outcomes were compared using Mann-Whitney U, Kruskal Wallis and Pearson's Chi-square test as appropriate. We identified 119 patients; 65 Whipples [Robotic Whipple (RW)], 43 distal pancreatectomies, 4 total pancreatectomies, 6 pancreatic enucleations, and 1 robotic cyst gastrostomy with a median age of 71 [24-91], median body mass index (BMI) of 27.6 (16.8-40.2), and American society of anesthesiologists (ASA) of 3. The median estimated blood loss (EBL) was 125 [25-800] and loss of heterozygosity (LOH) 6 [1-34]. Mean operative time for RW decreased after 15 cases (578 vs. 457 minutes, P<0.004). Conversions to open occurred in 5 (4.2%) patients. In total of 117 (98.3%) patients underwent R0 resections and the median lymph node (LN) harvest was 16 [0-37]. The 30 and 90 days mortality was 1 (0.8%). Major complications (Clavien-Dindo grade 3-5) were seen in 16 (13.4%) cases (20.3%) but decreased steadily as volume increased (case 30). Pancreatic leaks occurred in 14 (11.8%): A, 8 (6.7%); B, 4 (3.4%); and C, 2 (1.7%). Robotic assisted approaches to pancreatic resections is feasible. However, it takes approximately 15 cases before a decrease in operative time and 30 cases before major complications are decreased. These trends in complications are associated with surgeon experience and volume are critical to consider in robotic pancreatic surgery.

Single-Port Thoracoscopic Minimally Invasive Esophagectomy for Esophageal Cancer.

This study was to explore the safety and feasibility of single-port thoracoscopic esophagectomy for esophageal cancer. The patients were placed in left lateral prone position, and a 4-cm incision through the 4th-5th intercostal space was taken on the post-axillary line. Except for a surgical wound protector, no other special instruments were used for single-port technique. The 10-mm camera and two or three thoracoscopic instruments were used for the thoracic phase. Mobilization of stomach with celiac lymph node dissection was performed via multiple-port laparoscopic approach. Cervical double-layered anastomosis was completed by hand-sewn technique. A total of twenty-eight patients with esophageal squamous cell carcinoma underwent the single-port thoracoscopic surgery. All of the patients underwent R0 resection. The median time taken for thoracic phase and total operation time were 126min (range, 121-153) and the 253min (range, 197-309), respectively. The median number of resected thoracic lymph nodes was 16 (range, 12-24). There were no deaths or severe postoperative complications in this study, with no conversion of minimally invasive surgery to open procedure. Our preliminary results demonstrate that this technique is safe and feasible for treating esophageal cancer within an acceptable length of operation time, which does not compromise the surgical radicality.

Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A Pooled Analysis

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection, distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels. Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19-9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9 100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19-9 ≥353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001) correlated with worse OS. Patients treated with postoperative chemoradiation doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9 predicts both OS and pattern of failure. Therefore, CA19-9 should be included in predictive models in order to customize treatments based on prognostic factors. Moreover, future studies should stratify patients according to presurgical CA19-9 level.

Role of positive peritoneal lavage cytology in carcinoma gall bladder: a prospective observational study of 60 patients with the preoperative diagnosis

Introduction: Positive peritoneal lavage cytology ( PLC) in patients with carcinoma stomach is considered M1 disease according to AJCC classification (7th edition, 2010). Status of PLC positivity in carcinoma gall bladder (CGB) is untested yet. Method: The study included 60 patients who underwent treatment in PGIMER, Chandigarh, India (June 2015–July 2016). After staging laparoscopy (SL), abdomen was explored and 50ml of normal saline instilled in the peritumoral region, right paracolic gutter and pelvis. The lavage fluid was aspirated, mixed with an anticoagulant and spun to obtain a sediment that was subjected to Liquid Based Cytology. Papanicolaou and May Grunwald Giemsa slides were studied for malignant cells. During SL, if metastatic, lavage was done laparoscopically. When resectable, patients underwent R0 resection. Results: There were 25 resectable, 2 unresectable, 22 metastatic and 11 cases of xanthogranulomatous cholecystitis. 6 out of 49 CGB patients had positive PLC ( 12.2%).1 patient had resectable G3pT2N0M0 adenocarcinoma, 1 had unresectable celiac lymph nodal metastasis and 4 had peritoneal metastasis on SL. The median disease- specific survival for metastatic disease was 4 months. The same for resected population (negative PLC) was not reached. The disease-free survival of the only resected patient with positive PLC was 5 months, comparable to that of metastatic patients. The survival difference between patients with positive and negative PLC was not significant. Conclusion: Although positive PLC may suggest advanced disease, the correlation between PLC and survival or disease stage is not statistically significant yet.

MCL-1 expression of non-small cell lung cancer as a prognostic factor and MCL-1 as a promising target for gene therapy.

e24236 Background: MCL-1 is an important member in the pro-survival Bcl-2 family, plays a critical role in multidrug resistance. We investigated the significance for MCL-1 expression of non- small cell lung cancer (NSCLC) and the effect of inhibition of MCL-1 gene with siRNA (si-MCL-1) in NSCLC cells. Methods: Tumor tissues from 80 patients underwent R0 resection with NSCLC without any neoadjuvant therapy were analyzed. The intratumoral expressions of MCL-1 and Ki-67 were evaluated with immunohistochemistry in the tumor nucleus. Apoptotic index (AI) was defined as number of apoptotic cells, detected by TUNEL. Subsequently, we tested two MCL-1 overexpressing lung cancer cells, adenocarcinoma cell H358 and squamous carcinoma cell RERF, were used. Real-time RT-PCR was performed to evaluate gene expressions. The siRNA targeting MCL-1 (si-MCL-1) was transfected into cells. MTT assay was used to evaluate the cell viability and IC50. Results: The percentage of MCL-1 positive tumor nucleus varied greatly (median = 25.0%; mean±SD = 26.8±20.9%). A sample was classified as MCL-1 high tumor if > 25% of the nucleus in the tumor exhibited positive stainings. Among 80 patients with NSCLCs, 36(45.0%) were MCL-1 high status. The 5-year survival rate for patients with MCL-1 high tumors was significantly worse than that for patients with MCL-1 low tumors (68.3% vs. 93.1%, p = 0.0057). Regarding to the tumor proliferation, the Ki-67 index was significantly higher in the MCL-1 high tumor than that in MCL-1 low tumor (19.7±16.3% vs. 8.4±11.1%, p = 0.005). There was no significant relation between the AI and MCL-1 status. Si-MCL-1 effectively downregulated the MCL-1 expression (up to 80% at day 3) and significantly reduced the percentage of viable cells in these two cell lines as detected by MTT assay (p < 0.001, respectively). Multivariate analysis demonstrated MCl-1 expression to be a significant prognostic factor (hazard ratio, 4.069; p = 0.0405) Conclusions: MCL-1 expression is prognostic factor in NSCLC. The si-MCL-1 has an anti-proliferation effect against MCL-1-overexpressing NSCLC cells. MCL-1 appear to be a promising target for gene therapy.

Initiating a Robotic Program for Abdominal Surgery - Experiences from a Centre in Germany

Robotic systems are becoming increasingly important in abdominal surgery. We describe the implementation of a robotic program at a German centre for abdominal surgery, with focus on feasibility, safety, patient selection, learning curves, financial aspects and the lessons learned. This retrospective analysis covered data on patient demographics, intra- and postoperative parameters, oncological results and costs of all robotic-assisted abdominal operations performed at our institution between August 2012 to December 2016. It was also evaluated how possible factors for preoperative patient selection might influence intra- or postoperative outcome and learning parameters. 81 operations were performed - mostly colorectal resections (n = 35), ventral mesh rectopexy (n = 23) and liver resections (n = 18). The conversion rate was 7%. All oncological patients underwent R0 resection. Mean postoperative hospitalisation was 8.8 days; mean morbidity was 24%, with major complications (Clavien-Dindo > II) in 7%; mortality was 0%. BMI above 33.5 kg/m2 was associated with significantly higher morbidity (p = 0.024) and rate of major complications (p = 0.046), as well as a significantly longer hospitalisation (p = 0.009). Patients older than 65 years had significantly higher morbidity (p = 0.025). With increasing numbers of operations, time of surgery decreased (p = 0.001). The average cost of a robot-assisted operation, including hospital stay, was 15,221 €. The costs of robotic sigmoid resections or liver resections were higher (compared to the open approach: 106.8 and 62.8% higher, respectively, compared to the laparoscopic approach 93.5 and 66.5% higher, respectively). Robotic surgery is a safe approach. A crucial factor in the successful and safe performance of robotic assisted operations is proper patient selection, especially during the implementation period. The inevitable learning curve and the higher costs compared to open and laparocopic surgery must be respected and specialisation of the whole team is necessary.

Intrahepatic cholangiocarcinoma : Results after 84 resections

The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing worldwide. Surgical resection is the only curative treatment option. This study analyzed the prognostic factors after resection of ICC. A total of 84patients were surgically treated under potentially curative intent. Perihilar and distal cholangiocarcinomas were excluded. The 5‑year survival was analyzed with respect to tumor stage (TNM), number of lesions, complete surgical resection (R0), peritoneal carcinosis and postoperative complications. The 5‑year survival was 27% and 77% of patients underwent R0 resections. In the univariate analysis a Tstage >2, an N+ situation or an R+ resection as well as peritoneal and multilocular intrahepatic spread were associated with apoorer prognosis. Postoperative complications also negatively influenced survival. On multivariate analysis the absence of peritoneal spread, node-negative tumor stages, singular hepatic lesions and alow Tstage as well as the absence of complications were associated with improved survival. The prognosis of ICC is poor even after successful surgical resection. Well-known tumor characteristics such as TNM are relevant prognostic factors. Surgical resection is accompanied by postoperative complications (most frequently biliary), which negatively influence survival. Adjuvant strategies are urgently needed to improve long-term survival even after complete surgical resection.

Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma

BackgroundLymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC. MethodsPatients undergoing curative-intent (R0 or R1) resection for IHCC between 2004 and 2012 were identified within the US National Cancer Database. LN thresholds were evaluated using maximal chi-square testing and five-year overall survival was modeled using Kaplan–Meier and Cox regressions. Results57% (n = 1,132) of 2,000 patients had one or more LNs resected and pathologically examined. In the 631 patients undergoing R0 resection with pN0 disease, maximal chi-square testing identified ≥3 LNs as the threshold most closely associated with overall survival. Only 39% of resections reached this threshold. On multivariable survival analysis, no threshold of LNs was associated with overall survival, including ≥3 LNs (p = 0.186) and the current American Joint Committee on Cancer recommendation of ≥6 LNs (p = 0.318). ConclusionIn determining the extent of lymphadenectomy at the time of curative-intent resection for IHCC, surgeons should carefully consider the prognostic yield in the absence of overall survival benefit.

Cholangiocarcinoma: A Single-center Western Experience

Background: The purpose of this study was to summarize the surgical management and to evaluate survival rate and clinical outcome of cholangiocarcinoma, in patients hospitalized in our Unit of Oncology and General Surgery.Methods: This is a retrospective analysis of 76 consecutive patients with diagnosis of cholangiocarcinoma. The surgical procedure was selected based on the origin of the neoplasia. Tumor stage was defined according to the pathological tumour-node-metastasis classification (TNM 7th edtn, 2010). After resection, all patients underwent regular follow-up.Results: During the study period, 58 patients underwent explorative laparotomy. Forty-six patients were submitted to respective surgery with curative intent. A curative resection (R0) was achieved in 42/46 resected patients. The overall median survival time was 14.2 months, with 1, 3 and 5 year survival rates of 53.6%, 37.7%, and 19.6%, respectively. The survival rates, for the patients underwent R0 resection, was respectively 69%, 47.8% and 32.6% at 1, 3 and 5 years, with median survival time of 20.1 months.Conclusions: Our experience confirms the main role of R0 surgery in the curative treatment of cholangiocarcinoma.

Adjuvant chemotherapy provided survival benefit for stage T2N0 gastric cancer with high-risk factors

The value of adjuvant chemotherapy in T2N0 gastric cancer (GC) remains controversial. The aim of this retrospective study is to define a high-risk subgroup of pathological T2N0 GC patients and examine the impact of adjuvant chemotherapy on overall survival (OS). A total of 225 patients underwent R0 resection for T2N0 gastric adenocarcinoma between 2002 and 2012 and 51/225 (22.7%) of these received adjuvant chemotherapy. Multivariate Cox regression identified tumor location in the Upper1/3 of the stomach (peast one of the independent risk factor listed above, and we found that adjuvant chemotherapy significantly improved OS for this subgroup.

Robotic-assisted total mesorectal excision with the single-docking technique for patients with rectal cancer

BackgroundThe robotic system has advantages of high-definition three-dimensional vision and articular instruments with high dexterity, allowing more precise dissection in the deep and narrow pelvic cavity.MethodsWe enrolled 95 patients with stage I-III rectal cancer (adenocarcinoma) who underwent totally robotic-assisted total mesorectal excision (TME) with single-docking technique at a single institution between September 2013 and December 2016.ResultsOf the 95 patients, 48 (50.5%) and 30 (31.6%) patients had lower and middle rectal cancers, respectively. Of the 75 (78.9%) patients undergoing preoperative concurrent chemoradiotherapy (CCRT), 27 (28.4%) exhibited pathologic complete response (pCR). Only four (4.2%) patients underwent abdominoperineal resection and the sphincter preservation rate was 95.8%. R0 resection was performed in 92 (96.8%) patients. Circumferential resection margin (CRM) and distal resection margin (DRM) were positive in 2 (2.1%) and 1 (1.1%) patients, respectively. The anastomotic leakage rate was 5.4% (5/95 patients). The overall complication rate was 17.9% (17/95 patients); most of them were mild. No 30-day hospital mortality occurred, and no patients required conversion to open surgery. In 92 patients undergoing R0 resection, 2-year overall survival was 94% and 2-year disease-free survival was 83%.ConclusionsThe results demonstrated that totally robotic-assisted TME with the single-docking technique is safe and feasible for patients with rectal cancer, with or without preoperative CCRT. Moreover, favorable pCR rate, R0 resection rate, CRM, DRM, sphincter preservation rate, and short-term oncological outcomes can be achieved by combining this approach with appropriate preoperative CCRT.

Bronchial sleeve anastomosis and primary closures with the da Vinci system: an advanced minimally invasive technique

Background: Bronchial division using a stapler may lead to a positive or suboptimal bronchial margin during anatomical resections if the tumour is close to the lobar orifice. Primary suture closure of the bronchus, instead of stapling, or bronchial sleeve anastomosis may provide a better marginal distance in such cases. One of the advantages of minimally invasive robotic surgery (da Vinci System Intuitive Surgical, Sunnyvale, CA, USA) is the complete transfer of surgeon’s capability inside the thoracic cavity. In this study, we analysed primary bronchial closure or bronchial anastomosis techniques performed using robot-assisted thoracoscopic surgery (RATS). Methods: In total, 296 patients underwent robot-assisted thoracoscopy in our centre between January 2012 and June 2017. Among these, 203 underwent anatomical lung resections. Surgical bronchial closure techniques were performed on nine patients. The indications for bronchial closure, details of surgery and peri- and postoperative characteristics were analysed in this study. Results: We performed primary suture closure in three patients, sleeve lobectomy in five and isolated partial bronchotomy and bronchial closure in one. Although we used prolene sutures in the first three patients, we preferred to use V-loc sutures (barbed sutures; Medtronic, Covidien New Haven, CT, USA) in the more recent patients. The mean docking time was 16.3±5.8 min (range, 10–25 min), and the mean operation duration was 101.1±24.2 min. The duration of drainage was 3.6±1 days, and the mean length of postoperative stay in hospital was 6.2±1.6 days. All patients underwent R0 resections. Conclusions: Bronchial closure without staplers is a safe method in experienced hands in robotic surgery. Negative surgical margins of the bronchus can be achieved in lung tumours that are close or extending over the lobar bronchus by higher technical capabilities of robotic surgery. We believe V-loc sutures have a potential place in bronchial closure in minimally invasive surgery.