Does adjuvant treatment improve survival in R1 resected perihilar cholangiocarcinoma? The risk of overtreatment.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is associated with positive margins in up to half of the patients. It remains unclear whether adjuvant therapies contribute to improved survival in patients undergoing R1 resection for pCCA. METHODS: The National Cancer Database was queried for patients diagnosed with pCCA between 2004 and 2016. Patients with metastatic disease at the time of diagnosis were excluded. RESULTS: A total of 1756 patients were included (286 surgical patients and 1470 nonsurgical patients). Patients who underwent R0 resection showed a significantly better median overall survival (OS) than that of patients who underwent R1 resection (41.7 vs 21.4 months, respectively; P = .003). Nevertheless, OS was better in patients who underwent R1 resection than in nonsurgical patients (21.4 vs 6.3 months, respectively; P < .001). Patients undergoing chemoradiation after R1 resection had similar OS to that of those receiving any other adjuvant therapy (21.4 vs 19.4 months, respectively; P = .789) or no adjuvant treatment (21.4 vs 19.8 months, respectively; P = .925). After uni- and multivariable analyses, T stage ≥3 and R1 margins were independently associated with worse survival after surgery. CONCLUSION: As currently neither radiation, chemoradiation, nor chemotherapy seem to significantly improve survival in patients who underwent R1 resection for pCCA, high-quality surgical resection remains critically important. Moreover, the concern of overtreatment of patients who underwent R1 resection with current adjuvant therapeutic regimes exists.

Innovations in surgery for gallbladder cancer: A review of robotic surgery as a feasible and safe option.

BACKGROUND: This study evaluates the efficacy and safety of robotic-assisted surgical techniques in the treatment of gallbladder cancer, comparing it with traditional open and laparoscopic methods. METHODS: A systematic review of the literature searched for comparative analyses of patient outcomes following robotic, open, and laparoscopic surgeries, focusing on oncological results and perioperative benefits. RESULTS: Five total studies published between 2019 and 2023 were identified. Findings indicate that robotic-assisted surgery for gallbladder cancer is as effective as traditional methods in terms of oncological outcomes, with potential advantages in precision and perioperative recovery. CONCLUSIONS: Robotic surgery offers a viable and potentially advantageous alternative for gallbladder cancer treatment, warranting further research to confirm its benefits and establish comprehensive surgical guidelines.

Laparoscopic Dissection of Lymph Node Station 16-Why and How?

BACKGROUND: Dissection of para-aortic lymph nodes (Station 16) provides an important prognosticator for patients with gastrointestinal, colorectal, and hepatobiliary cancers.1-4 For example, a positive Station 16 lymph node has been shown to lead to 2-year survival of 3% in patients with pancreas adenocarcinoma, akin to stage IV disease.5,6 Thereby, Station 16 involvement can help with the risk/benefit stratification of the decision to move forward with radical surgery.7-9 Furthermore, it has been shown for gallbladder cancer that involvement of Station 16 cannot necessarily be predicted from the dissection of the hepatoduodenal ligament lymph nodes only.10,11 TECHNIQUE: With the patient in the French position, a complete Kocherization and a Cattel-Braasch maneuver is performed, allowing for visualization of LN station 16b. Station 16b is the inferior border of the station 16 compartment. The left renal vein (LRV) serves as an important landmark to identify the superior border of the dissection comprised by Stations 16a2 and 16b1. Station 16a2 dissection may be associated with a traction injury of the left renal vein or damage of right renal or suprarenal arteries and is dissected if there are specific concerns regarding involvement. CONCLUSIONS: While station 16 provides important prognostic information for risk stratification, a strategic and stepwise approach is needed for a safe sampling. This is accomplished by wide mobilization of the duodenum, implementation of thermal fusion to minimize chyle leak, and careful dissection below the left renal vein.

Subsegmental approaches to S7: anatomic laparoscopic transdiaphragmatic and nonanatomic robotic transthoracic.

BACKGROUND: Minimally invasive liver surgery of postero-superior segments (S4a, S7, S8) remains a challenge. The caudal view, an increased distance between trocars and the operative field, and the liver fulcrum limiting the view, contribute to the difficulty [1, 2]. We and other groups have previously reported the use of intercostal trocars to access subdiaphragmatic tumors (transdiaphragmatic approach) [3-5], only few reports on a laparoscopic total transthoracic approach, none (to our knowledge) dynamic manuscripts of a total transthoracic robotic approach, and none (to our knowledge) that use preoperative port site and anatomic modelling exist. Further, we developed a total transthoracic (thoracoscopic) approach to avoid a hostile abdomen, while bringing viewing axis and instruments close to the target [6-10]. In this context, this report details the advantages of a laparoscopic vs. robotic transthoracic approach. According to institutional protocol, reports of individual cases in print or video format do not require institutional review board approval. PATIENT: A 68-year-old male on peritoneal dialysis with left colon adenocarcinoma and a single synchronous liver metastasis in S6-7 close to the root of the right hepatic vein underwent a laparoscopic transdiaphragmatic metastasectomy. Two years later, the patient developed a recurrent 1.5 cm liver metastasis in S7, which lend itself to a robotic transthoracic approach. TECHNIQUE: Following 3-D modelling and virtual port placement planning, the first metastasectomy was performed laparoscopically using a transdiaphragmatic approach. The recurrence was managed transthoracically due to more apical, subdiaphragmatic location. For this operation, a robotic approach was optimal as robotic wrist articulation facilitates manipulation via the limited intercostal space. This was particularly helpful during the diaphragmatic reconstruction. CONCLUSIONS: Total transthoracic liver surgery is certainly an advanced procedure requiring superior MIS liver skills. Recommendations for starting with a total transthoracic approach are not unlike from starting a standard, none-transthoracic liver surgery. Early on in the experience we recommend advanced liver MIS skills, and single, small, subdiaphragmatic tumors away from major vessels. Nonetheless, when these recommendations are followed a total transthoracic approach may be safer and result in less access trauma, than traversing a hostile abdomen to reach the posterior-superior liver. Both laparoscopic and robotic transthoracic approaches can facilitate the resection of subdiaphragmatic tumors, especially in patients with hostile abdomens. While the laparoscopic approach has advantages due to a broader spectrum of available surgical tools (flexible tip camera, parenchymal dissection, and energy devices), the robotic wrist articulation facilitates manipulation via the restricted intercostal space.

Analysis of the Extent of Liver Oncological Extended Resection for Incidental Gallbladder Cancer: How Much Is Too Much?

BACKGROUND: Liver resection is pivotal in treating incidental gallbladder cancer (IGBC). However, the adequate volume of liver resection remains controversial. METHODS: A cross-sectional retrospective analysis was performed on resected IGBC patients between 1999 and 2018. Morbidity was evaluated according to the Clavien-Dindo classification. The theoretical volume of a 2-cm and 1.5-cm wedge liver resection was calculated (105 cm3 and 77.5 cm3, respectively) and used as reference. Overall survival (OS) was estimated using Kaplan-Meier and Cox regression analyses. RESULTS: Among 111 patients re-resected for IGBC, 84 provided sufficient data to calculate liver resection volume. Patients with a resection volume ≥ 105 cm3 had a higher rate of overall morbidity (P = 0.001) and length of stay (P = 0.012), with no difference in mortality. There was no significant difference in OS according to residual cancer or T-category. A resection volume ≥ 77.5 cm3 was more frequent in T ≥ 3 than in T1-2 patients (P = 0.026), and residual cancer was higher (P = 0.041) among patients with ≥ 77.5 cm3 resected. Cox multivariate regression showed that residual cancer (HR = 11.47, P < 0.001), perineural/lymphovascular invasion (HR = 2.48, P = 0.021), and Clavien-Dindo ≥ IIIa morbidity (HR = 5.03, P = 0.003) predict worse OS, but not liver volume resection. CONCLUSION: There are no significant differences in OS based on resected liver volume of IGBC, when R0 is achieved. There is a significant difference in morbidity and length of stay when liver wedges are ≥ 105 cm3, which is lost when analyzed by Clavien-Dindo ≥ IIIa. A 77.5-105 cm3 resection is indicated in ≥ T3 patients, minimizing morbidity risk, while addressing concerns of overall survival.

R1 pancreatic cancer patients benefit from chemoradiation when initiation of adjuvant therapy is delayed.

BACKGROUND: Adjuvant chemotherapy (AC) following pancreaticoduodenectomy (PD) for pancreas cancer (PDAC) has been demonstrated to improve survival. However, the optimal adjuvant treatment (AT) regimen for R1-margin patients remains unclear. This retrospective study investigates the impact of AC vs. adjuvant chemoradiotherapy (ACRT) on survival (OS). MATERIAL AND METHODS: The NCDB was queried for patients with PDAC who underwent PD between 2010 and 2018. Patients were divided into, (A) AC<60 days, (B) ACRT<60 days, (C) AC≥60 days, and (D) ACRT≥60 days. Kaplan-Meier survival analyses and Cox multivariable regression analyses were performed. RESULTS: Among 13 740 patients, median OS was 23.7 months. For R1 patients, median OS for timely AC and ACRT, and delayed AC and ACRT was 19.91, 19.19, 15.24, 18.96 months, respectively. While time of AC initiation was an insignificant factor for R0 patients (p = 0.263, CI 0.957-1.173), a survival benefit was found for R1 patients who received AC<60 vs. ≥60 days (p = 0.041, CI 1.002-1.42). Among R1 patients, administration of delayed ACRT achieves the same survival benefit of timely AC initiation (p = 0.074, CI 0.703-1.077). CONCLUSION: The study suggests value in ACRT for patients with R1 margins when delay of AT≥60 days cannot be avoided. Hence, ACRT may mitigate the negative impact of delayed AT initiation for R1-patients.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Colorectal cancer in young patients below screening age - Demographic and socioeconomic factors associated with incidence and survival.

BACKGROUND: While early onset colorectal cancer (EOCRC) has previously been defined as CRC in patients younger than age 50, recent screening guidelines have been lowered to 45. With more younger patients aged 45-50 are now being screened, incidence trend and outcomes of very early EOCRC (20-44) remains unclear. METHOD: Surveillance, Epidemiology, and End Results database was analyzed between 2006 and 2016 using Joinpoint tool to evaluate annual percentage change (APC) in incident rates, focusing on race/ethnicity and socioeconomic status (SES). Cancer specific survival (CSS) was assessed using univariate and multivariate analysis. RESULTS: 41,815 EOCRC patients met inclusion criteria. Incidence has increased significantly in both age groups (APC in age group 20-44 = 1.21 and 45-49 = 1.06). Increase incidence of very early EOCRC was observed in White and Hispanic racial/ethnic groups (ACP 1.68 and 2.63), as well as population from counties with high poverty, unemployment, language barrier, foreign born resident, and high school dropout rates (ACP 2.07, 1.87, 1.21, 1.28 and 2.02 respectively). Further, the 5-year CSS was worse in Black patients, and patients from counties with high poverty, unemployment and high school dropouts rates (Age group 20-44, 63.11%, 66.39%, 67.48% and 66.95% respectively). On multivariate analysis, living in high poverty counties was an independent risk factor for poorer CSS for very early EOCRC (HR 1.20, 95% CI 1.07-1.34, p = 0.002). Multivariate analysis was adjusted by sex, pathology type, site of disease, disease extension and surgical treatment history. CONCLUSION: Very early EOCRC incidence increases in White, Hispanic and poor patients, and outcomes are worse for minority and low-income patients. Further study on very early EOCRC is needed among those patients.

Trends in Preoperative Chemotherapy Utilization for Proximal Pancreatic Cancer: Are We Making Progress?

BACKGROUND: While it has been shown that neoadjuvant chemotherapy (NCT) for pancreatic cancer (PDAC) undergoing pancreaticoduodenectomy (PD) is critical for optimal oncologic management, NCT is (A) not universally practiced and (B) the reasons ill-defined. This study investigates national rates, trends, and factors affecting NCT utilization. PATIENTS AND METHODS: Using the National Cancer Database, patients who underwent PD for PDAC between 2006 and 2017 were identified. Changes in chemotherapy sequence over time were identified. For patients diagnosed after 2010, multivariable logistic regression models for factors affecting NCT were created. RESULTS: A total of 128,980 patients were diagnosed and 23,206 underwent surgery. Three thousand five (12.9%) received NCT with a preoperative chemotherapy (NCT + PCT) utilization rate of 7.3% in 2004 that increased to 36.8% in 2017. Factors affecting utilization of preoperative chemotherapy were age (OR 0.972), academic and integrated network institutions (OR 1.916, OR 1.559), institutional case volume (OR 1.007), distance from the hospital (OR 1.002), stage (IB OR 3.108, IIA OR 3.133, IIB OR 3.775, III OR 3.782), grade IV (OR 1.977), and insurance status (private OR 2.371, Medicaid OR 1.811, and Medicare OR 2.191, government OR 2.645). CONCLUSION: Even though more than 3/5 of patients receive no preoperative chemotherapy (NCT + PCT) and nearly 1/5 of patients still receive no chemotherapy at all, utilization of NCT is increasing. Moreover, since this study demonstrates that omission of NCT is associated with modifiable factors such as type of institution and health care disparity, mechanisms (reimbursement, policy) geared to change current national practice patterns may most immediately affect optimal oncologic management.

High-Quality Surgery for Gallbladder Carcinoma: Rare, Associated with Disparity, and Not Substitutable by Chemotherapy.

BACKGROUND: Oncologic surgery for T1b-T3 gallbladder carcinoma (GBC) consists of gallbladder fossa resection or bisegmentectomy IVb/V with negative margins and portal/retropancreatic lymphadenectomy. Frequency of high quality oncologic surgery, factors associated with its use, and the ability of chemotherapy to rescue low-quality surgery (LQS) remain unknown. METHODS: The NCDB was queried for patients diagnosed with stage I-III (T1b-T3) GBC undergoing curative-intent surgery from 2004 to 2016. These patients were divided into two groups based on receiving high quality surgery (HQS) or not; HQS was defined as cholecystectomy with partial hepatectomy, lymph node harvest ≥ 6, and negative margins. Logistic regression and Kaplan-Meier survival analyses were performed. RESULTS: A total of 3796 patients met inclusion criteria; only 364 (9.6%) met HQS criteria, and 3432 (90.4%) did not achieve HQS and were deemed low-quality surgery (LQS). HQS was associated with improved median overall survival (55.1 vs. 25.5 months, P < .001). Adjuvant chemotherapy (AC) was not able to rescue LQS with poorer survival compared to HQS without AC (27.9 vs 55.1 months, P < .001). Factors associated with HQS included private insurance (OR 1.809, P < .001), higher income (OR 1.380, P = .038), urban/rural residence (vs metropolitan) (OR 1.641, P = .001), higher education (OR 1.342, P = .031), Medicaid expansion states (OR 1.405, P = .005), stage 3 GBC (OR 1.642, P = .020), and reresection (OR 2.685, P < .001). Factors associated with LQS included older age (OR 0.974, P < .001), comorbidities (OR 0.701, P = .004), and laparoscopic approach (0.579, P < .001). Facility type incrementally improved HQS rate (integrated cancer network vs. comprehensive community, 9.8% vs. 6.1%, OR 1.694, P = .003; academic/research center vs. integrated cancer network, 14.9% vs. 9.8%, OR 1.599, P = .003). CONCLUSION: While HQS for GBC strongly improves survival, it is infrequently practiced. The newly identified factors that improve survival for GBC, such as centralization, open approach, and insurance coverage, are modifiable and, therefore, should be considered to achieve optimal outcomes.

Is minimally invasive surgery for large gastric GIST actually safe? A comparative analysis of short- and long-term outcomes.

INTRODUCTION: While minimally invasive surgery (MIS) is frequently utilized to remove small gastric gastrointestinal stromal tumors (GIST), MIS surgery for tumors ≥ 5 cm is currently not endorsed by national guidelines as standard of care due to concerns of safety and inferior oncologic outcomes. Hence this study investigates the perioperative and long-term outcomes of MIS for T3 gastric GIST measuring 5-10 cm. METHODS: The National Cancer Database (NCDB) 2017 was queried for gastric GIST measuring 5-10 cm or T3 category. Inclusion criteria were known: stage, size, comorbidities, grade, lymphovascular invasion, type of surgery, approach, conversion info, margin status, mitotic rate, neoadjuvant and adjuvant treatment, hospital stay, readmission, 30- and 90-day mortality, complete follow-up, type of institution, and hospital gastric surgery case volume. Binary logistic regression, linear regression models, and Kaplan-Meier survival analysis were used. RESULTS: In 3765 patients, mean tumor size was 67.3 mm; 26.3% MIS; and 73.8% open. Median hospital stay was shorter for MIS (4.77 vs 7.04 days, p < 0.001). There was no significant difference in incidence of R1 margins [2.9% MIS vs. 3.1% open (p = 0.143)], unplanned readmission [2.9% MIS and 4.1% open (OR 0.474 p = 0.025)], 30-day mortality [0.5% MIS vs 1.2% open (OR 0.325, p = 0.031)], and 90-day mortality [0.9% MIS vs 2.1% open (OR 0.478 p = 0.036)]. Cox regression models for OS showed no difference in survival (p = 0.137, HR 0.808). CONCLUSION: This analysis provides substantial evidence that MIS for gastric GIST ≥ 5-10 cm may not only offer improved postoperative morbidity but also oncologic safety. Moreover, as both approaches lead to similar long-term survival, national guidelines may need to incorporate this new information.

Treatment of Resectable Gallbladder Cancer.

Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors includes genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most common presentation of resectable gallbladder cancer, and surgery (minimally invasive or open) remains the only curative treatment available. Encouragingly, there is an important emerging role for systemic treatment for patients who have R1 resection or present with stage III-IV. In this article, we describe the pathogenesis, surgical and systemic treatment, and prognosis.