The impact of the COVID-19 pandemic on patients with pancreatic cancer.

BACKGROUND: It remains unclear today whether the poor prognosis of pancreatic ductal adenocarcinoma (PDAC) was further worsened by the COVID-19 pandemic and whether this may affect providers and patients, today. Hence, this study aimed to investigate the effect of COVID-19 on care delivery and outcomes of patients with PDAC in the United States. METHODS: The National Cancer Database was queried for PDAC, between 2017 and 2020. Changes in the number of diagnoses and treatment patterns were compared annually for the entire cohort. Changes in surgical outcomes and median time from diagnosis to treatment were compared and analyzed. Chi-square, Mann-Whitney U, and Kruskal-Wallis tests were performed. RESULTS: Of 127,613 patients with PDAC, PDAC diagnoses from 2017 (30,573) to 2019 (33,465) increased but decreased in 2020 (31,218). The number of patients receiving surgery or radiotherapy was stable between 2017 to 2019 (21.75% ± 0.05% and 13.9% ± 0.3%, respectively) but decreased in 2020 (20.7% and 12.4% respectively). Although patients received chemotherapy with increasing frequently from 2016 (60.7%) to 2019 (63.5%), this trend stopped in 2020 (63%). Of 27,490 patients undergoing surgery, the mean time from diagnosis to surgery increased from 2017 (34 days) to 2019 (56 days), with an increase in delay in 2020 (81 days). Moreover, patients who were tested for COVID-19, had a longer median time from diagnosis to surgery even if tested negative (COVID+, 140 days; COVID-, 112 days; P < .001). CONCLUSION: Although the oncologic quality of PDAC surgery remained the same during the pandemic, not only did the pandemic lead to an underdiagnosis of PDAC and care delays, but even the suspicion of COVID-19 in patients with a negative test adversely affected their care.

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.

Solid Pseudopapillary Tumor of the Pancreas: Is Enucleation Safe?

BACKGROUND: While solid pseudopapillary tumor (SPT) of the pancreas are oncologically low-risk tumors, their resection with pancreaticoduodenectomy (PD) or partial pancreatectomy (PP) carries a significant risk for morbidity. To balance the favorable prognosis with the surgical morbidity of pancreas resection, this study explores the oncologic safety of enucleation (EN). PATIENTS AND METHODS: The National Cancer Database (NCDB) was queried for resected SPT from January 2004 through December 2020. Perioperative outcomes and survival were analyzed with Kruskal-Wallis tests, and Kaplan-Meier analysis (with log-rank test). Survival analysis was performed to compare patients with and without lymph node (LN) metastases and binary logistic regression for predictors of LN metastasis. RESULTS: A total of 922 patients met inclusion criteria; 18 patients (2%) underwent EN, 550 (59.6%) underwent PP, and 354 (38.4%) underwent PD. Mean tumor size was 57.6 mm. Length of hospital stay was significantly shorter for EN compared with PP and PD groups (3.8 versus 6.2 versus 9.4 days, p < 0.001). There was a nonsignificant improvement in unplanned readmission [0% versus 8% versus 10.7% (p = 0.163)], 30-day mortality [0% versus 0.5% versus 0% (p = 0.359)], and 90-day mortality [0% versus 0.5% versus 0% (p = 0.363)] between EN, PP, and PD groups. Survival analyses showed no difference in OS when comparing EN versus PP (p = 0.443), and EN versus PD (p = 0317). Patients with LN metastases (p < 0.001) fared worse, and lymphovascular invasion, higher T category (T3-4) and M1 status were found as predictors for LN metastasis. CONCLUSIONS: EN may be considered for select patients leading to favorable outcomes. Because survival was worse in the rare cohort of patients with LN metastases, the predictors for LN metastasis identified here may aid in stratifying patients to EN versus resection.

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.

Global practice patterns of preoperative image reconstruction for liver surgery.

BACKGROUND: Three-dimensional (3-D) liver modeling is used globally; however, its actual practice is limited to a few centers. This study aimed to assess practice patterns and barriers to the use of 3-D modeling among liver surgeons worldwide. METHODS: A survey approved by the International Hepato-Pancreato-Biliary Association research council consisting of 27 questions was conducted using an online questionnaire. Incomplete responses were excluded. RESULTS: Of 235 respondents from 46 countries, 81.3% reported experience with 3-D modeling; however, only 21% used it in > 75% of cases. Surgeons using 3-D reconstruction were older (P = .025), worked more frequently at academic facilities (P = .007), and had more years of experience (P = .001), especially in minimally invasive liver surgery (MILS) (P = .038). In addition, 3-D rendering was performed by surgeons in 50.8% of cases. Liver volumetry was the most frequent indication (80.1%), and decreased postoperative complications were the main perceived benefit (53.6%). CONCLUSIONS: More experience in liver surgery because of seniority, case volume, and openness to novel technology (MILS) is associated with a greater appreciation for the value of 3-D modeling. Our results suggest the need for senior surgeons to help early-career surgeons consider 3-D modeling for the reported benefit of reduced intra- and postoperative complications.

Incidence of and Risk Factors for Incisional Hernia After Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Incisional hernia (IH) is common after major abdominal surgery; however, the incidence after hepatectomy for cancer has not been described. We analyzed incidence of and risk factors for IH after hepatectomy for colorectal liver metastases (CLM). METHODS: Patients who underwent open hepatectomy with midline or reverse-L incision for CLM at a single institution between 2010 and 2018 were retrospectively analyzed. Postoperative CT scans were reviewed to identify IH and the time from hepatectomy to hernia. Cumulative IH incidence was calculated using competing risk analysis. Risk factors were assessed using Cox proportional hazards model analysis. The relationship between IH incidence and preoperative body mass index (BMI) was estimated using a generalized additive model. RESULTS: Among 470 patients (median follow-up: 16.9 months), IH rates at 12, 24, and 60 months were 41.5%, 51.0%, and 59.2%, respectively. Factors independently associated with IH were surgical site infection (HR: 1.54, 95% CI 1.16-2.06, P = 0.003) and BMI > 25 kg/m2 (HR: 1.94, 95% CI 1.45-2.61, P < 0.001). IH incidence was similar in patients undergoing midline and reverse-L incisions and patients who received and did not receive a bevacizumab-containing regimen. The 1-year IH rate increased with increasing number of risk factors (zero: 22.2%; one: 46.8%; two: 60.3%; P < 0.001). Estimated IH incidence was 10% for BMI of 15 kg/m2 and 80% for BMI of 40 kg/m2. CONCLUSION: IH is common after open hepatectomy for CLM, particularly in obese patients and patients with surgical site infection. Surgeons should consider risk-mitigation strategies, including alternative fascial closure techniques.

Bile duct injury after cholecystectomy: timing of surgical repair should be based on clinical presentation. The experience of a tertiary referral center with Hepp-Couinaud hepatico-jejunostomy.

Impact of timing of repair on outcomes of patients repaired with Hepp-Couinaud hepatico-jejunostomy (HC-HJ) after bile duct injury (BDI) during cholecystectomy remains debated. This is an observational retrospective study at a tertiary referral hepato-biliary center. HC-HJ was always performed in patients without sepsis or bile leak and with dilated bile ducts. Timing of repair was classified as: early (≤ 2 weeks), intermediate (> 2 weeks, ≤ 6 weeks), and delayed (> 6 weeks). 114 patients underwent HC-HJ between 1994 and 2022: 42.1% underwent previous attempts of repair at referring institutions (Group A) and 57.9% were referred without any attempt of repair before referral (Group B). Overall, a delayed HC-HJ was performed in 78% of patients; intermediate and early repair were performed in 17% and 6%, respectively. In Group B, 10.6% of patients underwent an early, 27.3% an intermediate, and 62.1% a delayed repair. Postoperative mortality was nil. Median follow-up was 106.7 months. Overall primary patency (PP) attainment rate was 94.7%, with a 5- and 10-year actuarial primary patency (APP) of 84.6% and 84%, respectively. Post-repair bile leak was associated with PP loss in the entire population (odds ratio [OR] 9.75, 95% confidence interval [CI] 1.64-57.87, p = 0.012); no correlation of PP loss with timing of repair was noted. Treatment of anastomotic stricture (occurred in 15.3% of patients) was performed with percutaneous treatment, achieving absence of biliary symptoms in 93% and 91% of cases at 5 and 10 years, respectively. BDI can be successfully repaired by HC-HJ regardless of timing when surgery is performed in stable patients with dilated bile ducts and without bile leak.

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.

Neoadjuvant Treatments for Pancreatic Ductal Adenocarcinoma: Where We Are and Where We Are Going.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC. METHODS: A PubMed database search of articles published up to September 2022 was carried out. RESULTS: Many studies showed that FOLFIRINOX or Gemcitabine-nab-paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro-metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process. CONCLUSIONS: The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery.

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.

Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry.

BACKGROUND: Widespread use of minimally invasive liver surgery (MILS) contributed to the reduction of surgical risk of liver resection for hepatocellular carcinoma (HCC). Aim of this study was to analyze outcomes of MILS for single ≤3 cm HCC. METHODS: Patients who underwent MILS for single ≤3 cm HCC (November 2014 - December 2019) were identified from the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) Registry. RESULTS: Of 714 patients included, 641 (93.0%) were Child-Pugh A; 65.7% were limited resections and 2.2% major resections, with a conversion rate of 5.2%. Ninety-day mortality rate was 0.3%. Overall morbidity rate was 22.4% (3.8% major complications). Mean postoperative stay was 5 days. Robotic resection showed longer operative time (p = 0.004) and a higher overall morbidity rate (p < 0.001), with similar major complications (p = 0.431). Child-Pugh B patients showed worse mortality (p = 0.017) and overall morbidity (p = 0.021), and longer postoperative stay (p = 0.005). Five-year overall survival was 79.5%; cirrhosis, satellite micronodules, and microvascular invasion were independently associated with survival. CONCLUSIONS: MILS for ≤3 cm HCC was associated with low morbidity and mortality rates, showing high safety, and supporting the increasing indications for surgical resection in these patients.

Anatomic Laparoscopic Partial Hepatectomy of a Segment 4a B-Catenin Mutated Adenoma.

BACKGROUND: Although a ß-catenin mutated hepatocellular adenoma (HCA) is a benign liver tumor, it can cause bleeding, obstruction, pain, and hepatocellular carcinoma.1-3 Because surgery needs to balance these risks with its morbidity, a minimally invasive approach may be well suited.4-6 In this report, a strategic approach to minimally invasive resection of HCA encompassing segment 4a (S4a) is reviewed. PATIENT: A 22-year-old woman with abdominal pain was found to have two liver lesions involving segment 4a (5 cm) and segment 8 (S8) (4.5 cm). Liver biopsy confirmed a ß-catenin mutated HCA in the S4a lesion. After embolization, an anatomic S4a segmentectomy and a partial S8 resection were planned. TECHNIQUE: Three-dimensional modeling was used to perform a preoperative virtual hepatectomy; to visualize the spatial relationship between the HCA, the portal bifurcation, and the hepatic veins; and to preplan the port sites.7 With the patient in the French position, after port placement, intraoperative ultrasound was performed to identify the transection plane.8 The main left portal pedicle and Rex's recessus were exposed, and the branches of S4a were dissected out, clipped, and divided. Using ultrasound, the middle hepatic vein was exposed to define the lateral border of the dissection plane. CONCLUSION: Although a ß-catenin mutated HCA in S4a does not necessitate a formal segmentectomy, understanding the anatomic structures outlining its borders can facilitate the resection, especially for a large HCA. Virtual hepatectomy helps to achieve a detailed comprehension of the complex borders of segment 4a. Preoperative embolization can firm up the tumor and minimize the risk of intraoperative rupture from manipulation.