The efficacy of wrapping with polyglycolic acid mesh and fibrin glue in preventing clinically relevant pancreatic fistula after minimally invasive distal pancreatectomy (WRAP Study): study protocol for a multicenter randomized controlled trial in Japan.

BACKGROUND: Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. METHODS: This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). DISCUSSION: The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Caveolin-1 expression is a predictor of survival and recurrence patterns in resected pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVE: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1high vs. cCav1low) or cancer-associated fibroblasts (fCav1high vs. fCav1low). RESULTS: Among all 615 patients, 40.7% were cCav1high and 72.7% were fCav1high. cCav1high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1low, and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1high patients with NAC showed better OS than those without, while there was no significant difference between cCav1low patients with NAC and those without. cCav1high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1high as an independent predictor of liver metastasis. CONCLUSIONS: cCav1high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.

Development of the multiple scope transition method in robotic pancreaticoduodenectomy.

BACKGROUND: Since robotic pancreaticoduodenectomy (R-PD) has emerged as a promising technique for treating periampullary tumors, optimal surgical views across various stages of the surgery are vital. This study aimed to describe the evolution and optimization of the multiple scope transition (MST) method using comprehensive videos and illustrations, particularly from the perspective of the patient-side assistants, to enhance the efficiency and safety of R-PD through its different phases. METHODS: We retrospectively analyzed 61 patients who underwent R-PD from April 2021 to May 2023. RESULTS: The median total operation duration was 599 min (415-840 min). The median scope transition times for redocking from the left to central lower position, transition from the central lower to upper position, and port-hopping from the central to right position were 169 s (53-725 s), 55 s (26-165 s), and 120 s (41-260 s), respectively. Owing to the advancements in the scope transition procedures, these scope transition times became shorter with an increase in the number of experiences. No intraoperative complications relevant to scope transition was reported, and the incidence of significant postoperative complications greater than Grade IIIa of the Clavien-Dindo classification was 8.2%. CONCLUSION: We reported the established role and evolution of the MST method from the standpoint of the patient-side assistants. The comfortable surgical field expansion provided by the MST method can ensure the safe and widespread application of R-PD.

Low incidence of pancreatic fistula and well-preserved endocrine function with non-reconstructed small remnant pancreas after pancreaticoduodenectomy.

Aim: Pancreatic reconstruction after pancreaticoduodenectomy (PD) that leaves a small remnant pancreas is often difficult. Pancreatic fistula is a major complication after PD, and fistulas are rare in patients with hard pancreas. However, the clinical impact of non-reconstructed small remnant after PD with hard pancreas is unknown. Methods: We included all patients who underwent PD for pancreatic tumor without pancreatic reconstruction in two institutions supervised by one surgeon between January 2004 and March 2021. Their short- or long-term outcome after surgery was retrospectively analyzed. Results: PD was performed in 774 patients, of whom 16 patients were without reconstruction (2.1%) with negative margins at the pancreatic stump. Pancreatic transection was performed above or to the left of the superior mesenteric artery, with a median remnant pancreas length of 3.7 cm (range, 1.3-10.0). A major complication (≥ Clavien-Dindo Grade IIIa) occurred in one patient (6%). Fistula of grade B occurred in one patient (6%). After a median follow-up of 44 months (95%CI, 10.6-77.3), insulin administration was unnecessary in 11 patients. Conclusion: The preservation of a small pancreatic remnant without reconstruction after PD can be performed safely and may enable the keeping of pancreatic endocrine function for some selected patients with hard pancreas.

Integrating surgical intervention and watch-and-wait approach in dMMR metastatic rectal cancer with pembrolizumab: a case report.

BACKGROUND: Treating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab. CASE PRESENTATION: A 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis. CONCLUSIONS: The WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer.

Robot-Assisted Pancreaticoduodenectomy with Hemicircumferential Dissection of Nerve Plexus Around the Superior Mesenteric Artery.

BACKGROUND: Pancreatic head cancer with perineural invasion of the superior mesenteric artery (SMA) requires dissection of the nerve plexus around the SMA (PLsma, superior mesenteric nerve plexus) to obtain cancer-free margins.1,2 Technically challenging robot-assisted pancreaticoduodenectomy with PLsma resection is rarely performed owing to the technical limitations of the robot. In this multimedia article, we present our approach to robot-assisted pancreaticoduodenectomy with PLsma dissection.3-5 METHODS: We performed a robot-assisted pancreaticoduodenectomy with resection of the hemicircle of the PLsma in a 78-year-old woman with resectable pancreatic cancer extending to the root of the inferior pancreaticoduodenal artery. In this video, we show how to obtain an optimal view using the multiple scope transition method,4 and technical tips to perform a PLsma dissection with a robot to perform this difficult surgery safely. RESULTS: The operative time was 568 min and 300 mL of blood was lost. The pathological diagnosis was invasive pancreatic ductal carcinoma with lymph node metastasis, and R0 resection was performed. The distance margin from the SMA was 2 mm. The patient was discharged on the 18th postoperative day without postoperative complications. CONCLUSIONS: Robot-assisted pancreaticoduodenectomy with dissection of the hemicircle of the PLsma, which is difficult to perform, can be performed safely with an optimal view using the multiple-scope transition method, and delicate dissection using a robot.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy.

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Scope transition and early arterial inflow control provide safe and comfortable dissection in robotic distal pancreatectomy.

PURPOSE: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery. METHODS: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position. RESULTS: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046). CONCLUSION: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP.

Management of potential portal vein thrombus during laparoscopic right hemihepatectomy following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is often performed prior to right hemihepatectomy (RH) to increase the future liver remnants. However, intraoperative removal of portal vein thrombus (PVT) is occasionally required. An algorithm for treating the right branch of the PV using laparoscopic RH (LRH) after PVE is lacking and requires further investigation. METHODS: In our department, after the confirmation of a lack of extension of PVT to the main portal trunk or left branch on preoperative examination (ultrasound and contrast-enhanced computed tomography), a final evaluation was performed using intraoperative ultrasonography (IOUS). Here we present the cases of eight patients who underwent LRH after PVE and examine the safety of our treatment strategies. RESULTS: IOUS revealed PVT extension into the main portal trunk in two cases. For the other six patients without PVT extension, we continued the laparoscopic procedure. In contrast, in the two cases with PVT extension, we converted to laparotomy after hepatic transection and removed the PVT. The median operation time for hepatectomy was 562 min (421-659 min), the median blood loss was 293 mL (85-1010 mL), no liver-related postoperative complications were observed, and the median length of stay was 10 days (6-34 days). CONCLUSIONS: PVT evaluation and removal are important in cases of LRH after PVE. Our strategy is safe and IOUS is particularly useful for laparoscopically evaluating PVT extension.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Technical Strategy for Pancreatic Body Cancers: A Raison d'etre of Distal Pancreatectomy with Portal Resection.

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.

Neoadjuvant chemotherapy for borderline resectable colorectal cancer liver metastases: a single-institution retrospective study.

INTRODUCTION: This study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy. MATERIALS AND METHODS: Since 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data. RESULTS: Of 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified. CONCLUSION: In patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.

Unique Biology of Pancreatic Ductal Adenocarcinoma Accompanied by Rapidly Impaired Diabetes: A Favorable Long-Term Survival Following Curative Resection.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained. METHODS: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated. RESULTS: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01). CONCLUSIONS: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.

Laparoscopic dissection around the superior mesenteric artery by left posterior approach during pancreaticoduodenectomy.

BACKGROUND: In pancreaticoduodenectomy (PD), the approach to superior mesenteric artery (SMA) is a critical process that supports adequate surgical margins and radicality for pancreatic tumors. In most of the reports on laparoscopic PD, the right-sided approach in which the jejunum is pulled out to the right side for peri-SMA dissection is used, since the left side of the SMA is difficult to dissect, and the only way to do this is to dissect the vein first. METHODS: We devised a method to simplify and safely perform peri-SMA dissection by reversing the process, starting from the left side of the SMA. The first step involves the mobilization of the pancreatic head, which allows for rotation around the SMA. The second step involves the dissection of the left side of the SMA and transection of the jejunum. The key point is to change the incision line between the anterior and posterior mesojejunum. The third process includes the inferior pancreatoduodenal artery (IPDA) and first jejunal artery (J1A) dissection, which can be easily performed from the left side because the SMA rotates by simply continuing the dissection along the previously exposed SMA, and the IPDA/J1A are safely dissected at the root because they are drawn to the left side. The remaining processes are performed on the right side. RESULTS: This method was performed in 16 cases, and in most cases IPDA/J1A were divided from the left side. CONCLUSION: The technique for SMA dissection from the left posterior side was described with illustrations and video. Our method allows safe oncologic dissection around SMA avoiding anatomical misorientation during laparoscopic PD.