Long-term outcomes and risk factors of pancreatic insufficiency after a pancreatoduodenectomy: A retrospective study.

BACKGROUND: An increasing number of patients are achieving long-term survival after pancreatoduodenectomy, meaning that risk assessments of endocrine and exocrine pancreatic insufficiency are needed. Herein, we investigated the risk factors for pancreatic insufficiency after pancreatoduodenectomy by incorporating pancreatic morphologic changes and perioperative factors. METHODS: Patients who underwent pancreatoduodenectomy between January 2015 and December 2020 were enrolled in this single-center retrospective study. Clinicopathologic, surgical, and pancreatic morphologic factors were collected, and risk factors for exocrine pancreatic insufficiency and endocrine pancreatic insufficiency were analyzed. Exocrine pancreatic insufficiency was defined as steatorrhea requiring pancreatic enzymes and new onset steatosis, and endocrine pancreatic insufficiency was defined as postoperative new-onset diabetes mellitus. Multivariate analysis was performed. RESULTS: Among the 206 patients enrolled, 14% and 24% developed endocrine pancreatic insufficiency and exocrine pancreatic insufficiency, respectively. Multivariate analysis revealed residual pancreatic stent 1 year postoperatively, lymph node metastasis, and postoperative pancreatic atrophy (P-atrophy) as independent risk factors for exocrine pancreatic insufficiency, whereas preoperative glycated hemoglobin levels, residual pancreatic stent, and postoperative main pancreatic duct dilatation were risk factors for endocrine pancreatic insufficiency. Subgroup analysis of pancreatic ductal adenocarcinoma revealed that exocrine pancreatic insufficiency in patients with pancreatic ductal adenocarcinoma was caused by preoperative decreased pancreatic function (high glycated hemoglobin and a low postoperative pancreatic fistula rate), whereas the high incidence of POPF influenced the development of exocrine pancreatic insufficiency in patients without pancreatic ductal adenocarcinoma. CONCLUSION: Postoperative pancreatic atrophy and main pancreatic duct dilatation are risk factors for exocrine pancreatic insufficiency I and endocrine pancreatic insufficiency, respectively, and residual pancreatic stent affects both types of pancreatic dysfunction. Improving the surgical approach and stent management may help prevent these late complications.

Outcomes after laparoscopic or open liver resection for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: a propensity score-matching study.

BACKGROUND: Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. METHODS: We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. RESULTS: Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). CONCLUSIONS: LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR.

New approach of circumferential lymph node dissection around the superior mesenteric artery for pancreatic cancer during pancreaticoduodenectomy (with video).

PURPOSE: Various approaches have been reported for the resection of the nervous and lymphatic tissues around the superior mesenteric artery (SMA) during pancreaticoduodenectomy (PD) for pancreatic cancer. We developed a new procedure for circumferential lymph node dissection around the SMA to minimize local recurrence. METHODS: We included 24 patients who underwent PD with circumferential lymph node dissection around the SMA (circumferential dissection) and 94 patients who underwent classical mesopancreatic dissection (classical dissection) between 2019 and 2021. The technical details of this new method are described in the figures and videos, and the clinical characteristics and outcomes of this technique were compared with those of classical dissection. RESULTS: The median follow-up durations in the circumferential and classical dissection groups were 39 and 36 months, respectively. The patients' characteristics, including tumor resectability, preoperative and adjuvant chemotherapy rates, postoperative complication rates, and tumor stage, were similar between the two groups. No differences were observed in recurrence-free survival and overall survival between the two groups; however, the classical dissection group tended to have more local recurrences than the circumferential dissection group (8.3% vs. 33.3%, P = 0.168). Although no case of nodular-type recurrence after circumferential dissection was observed, 61.1% of local recurrences after classical dissection were of the nodular-type, and 36.4% were located on the left side of the SMA. CONCLUSIONS: Performing circumferential lymph node dissection around the SMA during PD can be conducted safely with minimal risks of local recurrence and may enhance the completeness of local resection.

Short- and long-term outcomes of laparoscopic liver resection for non-alcoholic fatty liver disease-associated hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: We compared the recurrence-free survival (RFS), overall survival (OS), and safety of laparoscopic liver resection (LLR) between non-alcoholic fatty liver disease (NAFLD) and non-NAFLD hepatocellular carcinoma (HCC) patients. METHODS: Patients with HCC (n = 349) were divided into four groups based on the HCC etiology (NAFLD [n = 71], hepatitis B [n = 27], hepatitis C [n = 187], alcohol/autoimmune hepatitis [AIH] [n = 64]). RFS and OS were assessed by multivariate analysis after adjustment for clinicopathological variables. A subgroup analysis was performed based on the presence (n = 248) or absence (n = 101) of cirrhosis. RESULTS: Compared with the NAFLD group, the hazard ratios (95% confidence intervals) for RFS in the hepatitis B, hepatitis C, and alcohol/AIH groups were 0.49 (0.22-1.09), 0.90 (0.54-1.48), and 1.08 (0.60-1.94), respectively. For OS, the values were 0.28 (0.09-0.84), 0.52 (0.28-0.95), and 0.59 (0.27-1.30), respectively. With cirrhosis, NAFLD was associated with worse OS than hepatitis C (P = 0.010). Without cirrhosis, NAFLD had significantly more complications (P = 0.034), but comparable survival than others. DISCUSSION: Patients with NAFLD-HCC have some disadvantages after LLR. In patients with cirrhosis, LLR is safe, but survival is poor. In patients without cirrhosis, the complication risk is high.

Feasibility of laparoscopic radical antegrade modular pancreatosplenectomy (RAMPS) as a standard treatment for distal resectable pancreatic cancer.

INTRODUCTION: Laparoscopic (Lap-) radical antegrade modular pancreatosplenectomy (RAMPS) is an attractive radical procedure that aims to achieve negative posterior retroperitoneal margin in pancreatic ductal adenocarcinoma (PDAC) resections. However, only few institutions are adapting Lap-RAMPS due to the technical difficulties and the lack of supporting evidence for the clinical applications. METHODS: A retrospective cohort study was performed on consecutive patients who underwent RAMPS for distal resectable PDACs. We analyzed the short- and long-term outcomes including local control and the induction of adjuvant chemotherapy compared between Lap- and Open-RAMPS. RESULTS: Of the 118 RAMPS patients, 43 patients underwent Lap-RAMPS and 75 patients underwent Open-RAMPS. The blood loss was lower (125 vs. 390 mL, p < 0.001), and postoperative hospital stay was shorter (17 vs. 21 days, p = 0.018) in the Lap-RAMPS group. There was no difference in the postoperative complications and no mortality in both groups. R0 resection rate was 100.0% in the Lap-RAMPS and 90.7% in the Open-RAMPS (p = 0.039). Among the patients eligible for adjuvant chemotherapy, the Lap-RAMPS group showed a favorable induction rate (100.0 vs. 89.6%, p = 0.037). Both groups showed a favorable 3-year local recurrence rate (8.7 vs. 10.0%, p = 0.976) and 3-year overall survival (69.8 vs. 71.1%, p = 0.996). CONCLUSIONS: The safety and efficacy of Lap-RAMPS were comparable to those of Open-RAMPS in terms of achieving local control and adjuvant chemotherapy induction. A higher early induction of adjuvant chemotherapy is an advantage of minimally invasive surgery.

Treatment Strategy of Pancreas-Sparing Distal Duodenectomy for Distal Duodenal Malignancies with Adjustable Dissection Levels According to Disease Progression (with Video).

BACKGROUND: Pancreas-sparing distal duodenectomy (PSDD) is a favorable option for distal duodenal neoplasms, and its procedure, including the extent of lymphadenectomy, should be modified according to the malignancy of the tumor. However, there are no coherent reports on the details of this procedure or long-term outcomes after each resection. METHODS: This study included 24 patients who underwent PSDD at our institution between January 2009 and October 2020. Patients were divided into two groups according to the tumor progression: nine with (Lv-II) and fifteen without (Lv-I) mesopancreas dissection. Postoperative outcomes were compared between the two groups. RESULTS: Two groups had similar operation times, blood loss, hospital stay, and the rate of delayed gastric emptying (DGE): 40% versus 44%. There were no Clavien-Dindo classification ≥ III complications in the Lv-II group. The Lv-II group had a larger number of examined lymph nodes (median: 29), and three (33%) patients had lymph node metastasis. No local recurrence was observed, although two patients in the Lv-II group had liver metastasis. The 5-year overall survival rates of the Lv-I and Lv-II groups were 100% and 78%, respectively. None of the patients had an impaired nutrition status after one year of surgery, and no rehospitalization was observed in either group. CONCLUSION: Although PSDD with or without mesopancreas dissection entailed a high risk of DGE, this procedure showed favorable long-term outcomes and may be an alternative to pancreatoduodenectomy in patients with distal duodenal neoplasms.

RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer.

The invasiveness of pancreatic cancer and its resistance to anticancer drugs define its malignant potential, and are considered to affect the peritumoral microenvironment. Cancer cells with resistance to gemcitabine exposed to external signals induced by anticancer drugs may enhance their malignant transformation. Ribonucleotide reductase large subunit M1 (RRM1), an enzyme in the DNA synthesis pathway, is upregulated during gemcitabine resistance, and its expression is associated with worse prognosis for pancreatic cancer. However, the biological function of RRM1 is unclear. In the present study, it was demonstrated that histone acetylation is involved in the regulatory mechanism related to the acquisition of gemcitabine resistance and subsequent RRM1 upregulation. The current in vitro study indicated that RRM1 expression is critical for the migratory and invasive potential of pancreatic cancer cells. Furthermore, a comprehensive RNA sequencing analysis showed that activated RRM1 induced marked changes in the expression levels of extracellular matrix­related genes, including N­cadherin, tenascin­C and COL11A. RRM1 activation also promoted extracellular matrix remodeling and mesenchymal features, which enhanced the migratory invasiveness and malignant potential of pancreatic cancer cells. The present results demonstrated that RRM1 has a critical role in the biological gene program that regulates the extracellular matrix, which promotes the aggressive malignant phenotype of pancreatic cancer.

Lingual nerve impairment/injury after retrieval of the displaced mandibular third molar into the floor of the mouth.

Retrieval of the displaced mandibular third molar in the floor of the mouth is challenging as the lingual nerve is always at risk of injury. However, there are no available data to show the incidence of the injury caused by the retrieval. The goal of this review article is to provide the incidence of the iatrogenic lingual nerve impairment/injury caused by the retrieval based on the review of the existing literature. The retrieval cases were collected with the search words below using PubMed, Google Scholar, and CENTRAL Cochrane Library database on October 6, 2021. A total of 38 cases of lingual nerve impairment/injury in 25 studies were eligible and reviewed. Temporary lingual nerve impairment/injury due to retrieval was found in six cases (15.8%) and all recovered between three to six months after retrieval. General anaesthesia and local anaesthesia were used for retrieval in three cases each. The tooth was retrieved using a lingual mucoperiosteal flap in all six cases. The permanent iatrogenic lingual nerve impairment/injury due to retrieval of the displaced mandibular third molar is considered extremely rare as long as the appropriate surgical approach is chosen based on surgeons' clinical experience and anatomical knowledge.

Diagnosis and management of postpancreatectomy hemorrhage: A single-center experience of consecutive 1,096 pancreatoduodenectomies.

BACKGROUND/OBJECTIVES: This study aimed to assess the outcomes and characteristics of post-pancreatectomy hemorrhage (PPH) in over 1000 patients who underwent pancreatoduodenectomy (PD) at a high-volume hepatopancreaticobiliary center. METHODS: This retrospective study analyzed consecutive patients who underwent PD from 2010 through 2021. PPH was diagnosed and managed using our algorithm based on timing of onset and location of hemorrhage. RESULTS: Of 1096 patients who underwent PD, 33 patients (3.0%) had PPH; incidence of in-hospital and 90-day mortality relevant to PPH were one patient (3.0%) and zero patients, respectively. Early (≤24 h after surgery) and late (>24 h) PPH affected 9 patients and 24 patients, respectively; 16 patients experienced late-extraluminal PPH. The incidence of postoperative pancreatic fistula (p < 0.001), abdominal infection (p < 0.001), highest values of drain fluid amylase (DFA) within 3 days, and highest value of C-reactive protein (CRP) within 3 days after surgery (DFA: p < 0.001) (CRP: p = 0.010) were significantly higher in the late-extraluminal-PPH group. The highest values of DFA≥10000U/l (p = 0.022), CRP≥15 mg/dl (p < 0.001), and incidence of abdominal infection (p = 0.004) were identified as independent risk factors for PPH in the multivariate analysis. Although the hospital stay was significantly longer in the late-extraluminal-PPH group (p < 0.001), discharge to patient's home (p = 0.751) and readmission rate within 30-day (p = 0.765) and 90-day (p = 0.062) did not differ between groups. CONCLUSIONS: Standardized management of PPH according to the onset and source of hemorrhage minimizes the incidence of serious deterioration and mortality. High-risk patients with PPH can be predicted based on the DFA values, CRP levels, and incidence of abdominal infections.

Comparison of the clinical efficacy of a new prognostic stratification for duodenal adenocarcinoma with that of TNM staging: The importance of T status with regard to the prognosis.

BACKGROUND: Although the current staging system and therapeutic strategy for duodenal adenocarcinoma (DA) focus on the N status, their validity has not been clarified. In this study, we evaluated the prognostic factors of DA and reviewed the current staging system. METHODS: We included 105 patients who underwent surgical resection of DA in our department between September 2006 and October 2020. Patients with localised disease other than an early tumour (pT1a) were classified into the advanced group, and prognostic factors were compared with those for the Union for International Cancer Control (UICC) classification, 8th edition. RESULTS: The 5-year overall survival (OS) rate in the advanced group (n = 55) was 73%. Multivariate analysis revealed that pT4 and pN2 statuses were independent prognostic factors for OS. The prognosis was stratified based on the pT4 and pN2 statuses, whereas the survival curves for patients with pStage II (pN0) and pStage IIIA (pN1) DA overlapped on staging according to the UICC classification. The new classification indicated a favourable prognosis for patients classified as pT1-3N1 stage IIIA (5-year OS, 86%), whereas the prognosis of patients with pT4N0-1 DA was similar to those classified as pT1-3N2 stage IIIB. Patients with pT4N2 DA had a similar prognosis (5-year OS, 24%) as those with metastases, and 75% of these patients showed distant metastasis within one year after surgery. CONCLUSION: Both T and N statuses affect the prognosis of DA. Patients with pT4N2 DA may require intensive adjuvant chemotherapy. (238 words).

Evaluation of local recurrence after pancreaticoduodenectomy for borderline resectable pancreatic head cancer with neoadjuvant chemotherapy: Can the resection level change after chemotherapy?

BACKGROUND: Neoadjuvant treatment has significant survival benefits for patients with pancreatic cancer. However, local recurrence remains a serious issue, even after neoadjuvant treatment. This study investigated local recurrence after pancreaticoduodenectomy and determined the optimal resection level after neoadjuvant treatment. METHODS: This retrospective study analyzed consecutive patients who underwent pancreaticoduodenectomy for borderline resectable pancreatic cancer after 4 cycles of neoadjuvant treatment-gemcitabine plus nab-paclitaxel between April 2015 and March 2020. Patients with borderline resectable-artery pancreatic cancer were classified according to the dissection level around the artery: level 3 group, hemi-, or whole circumferential arterial nerve plexus was dissected; and level 2 group, the nerve plexus was preserved. RESULTS: Fifty-six patients with borderline resectable-artery pancreatic cancer underwent pancreaticoduodenectomy after neoadjuvant treatment (level 3 group, n = 40; level 2 group, n = 16). The resection level in the level 2 group was changed based on post-neoadjuvant treatment computed tomography images or intraoperative frozen section diagnosis. The overall and local recurrence rates were significantly higher in the level 2 group than in the level 3 group (overall recurrence, 93.8% vs 70.0%; P = .037) (local recurrence, 50.0% vs 5.0%; P < .001). Ten patients experienced local recurrence, of which 8 belonged to the level 2 group. Among them, 4 patients were confirmed as cancer-negative by surgical margin analysis or intraoperative frozen section diagnosis but experienced recurrence around the arteries. CONCLUSION: For treating borderline resectable-artery pancreatic cancer, changing the resection level based on post-neoadjuvant treatment computed tomography images increased the risk of local recurrence. All patients with borderline resectable-artery should undergo level 3 dissection, regardless of the response to neoadjuvant treatment.

Differences in periodontal parameters between SPT patients who regularly and irregularly visited the dental clinic analyzed at tooth level: a 14-year retrospective cohort study.

The purpose of this study was to evaluate the periodontal status of patients who routinely did SPT, when compared to patients that did not SPT. This retrospective cohort study was conducted at a general dental office from 2001 to 2019. Patients aged 18 to 81 years who visited the dental office over a 10-year period were assigned into two groups: an SPT group, which included patients who continually visited the dental office for SPT one or more times every year, and an irregular group, consisting of patients who did not visit the dental office at least once a year. A total of 7307 teeth (SPT group) and 4659 teeth (irregular group) were evaluated, and the periodontal conditions were compared between the first and latest visits. Multiple regression analysis was used to analyze the results. The mean follow-up time was 13.74 years. The risk factors for improvements in probing pocket depth included age, sex, smoking, diabetes mellitus, molar tooth, and irregular SPT group (p < 0.001), and that for a positive bleeding on probing site was the irregular group (odds ratio 2.94; 95% confidence interval 2.63-3.29). This study showed that lack of routine in attending the SPT program significantly decreased the periodontal parameters, thus highlighting the importance of continuing with the program to maintain the periodontal health.

Influence of Child-Pugh B7 and B8/9 cirrhosis on laparoscopic liver resection for hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in patients with Child-Pugh A cirrhosis has been shown to be beneficial. However, less is known regarding the outcomes of such treatment in patients with Child-Pugh B cirrhosis. We conducted a retrospective study to evaluate the outcomes of laparoscopic liver resection for HCC in patients with Child-Pugh B cirrhosis, focusing on surgical risks, recurrence, and survival. METHODS: 357 patients with HCC who underwent laparoscopic liver resection from 2007 to 2021 were identified from our single-institute database. The patients were divided into three groups by their Child-Pugh score: the Child-Pugh A (n = 280), Child-Pugh B7 (n = 42), and Child-Pugh B8/9 groups (n = 35). Multivariable Cox regression models for recurrence-free survival (RFS) and overall survival (OS) were constructed with adjustment for preoperative and postoperative clinicopathological factors. RESULTS: The Child-Pugh B8/9 group had a significantly higher complication rate, but the complication rates were comparable between the Child-Pugh B7 and Child-Pugh A groups (Child-Pugh A vs. B7 vs. B8/9: 8.2% vs. 9.6% vs. 26%, respectively; P = 0.010). Compared with the Child-Pugh A group, the risk-adjusted hazard ratios (95% confidence intervals) in the Child-Pugh B7 and B8/9 groups for RFS were 1.39 (0.77-2.50) and 3.15 (1.87-5.31), respectively, and those for OS were 0.60 (0.21-1.73) and 1.80 (0.86-3.74), respectively. There were no significant differences in major morbidities (Clavien-Dindo grade > II) (P = 0.117) or the proportion of retreatment after HCC recurrence (P = 0.367) among the three groups. CONCLUSION: Among patients with HCC, those with Child-Pugh A and B7 cirrhosis can be good candidates for laparoscopic liver resection in terms of complications and recurrence. Despite poor postoperative outcomes in patients with Child-Pugh B8/9 cirrhosis, laparoscopic liver resection is less likely to interfere with retreatment and can be performed as part of multidisciplinary treatment.

Application of Medical Imaging and 3D Printing Technology in Teaching the Handling of Novel Medicine in Periodontal Surgery.

Recently, fibroblast growth factor-2 (FGF-2) agents for periodontal tissue regeneration have been increasingly applied to the treatment of periodontal disease. Our current challenge for resident dentists with little clinical experience is to enhance instruction in the handling of new medicine in addition to teaching conventional procedures in periodontal tissue regeneration. This report describes using case-specific, cost-effective three-dimensional (3D) models for dentists' lectures and periodontal surgical training. As an educational and training aid, preoperative and postoperative cone-beam computed tomography images were superimposed to enable three-dimensional observation of postoperative bone regeneration. A three-dimensional anatomical model was fabricated based on these images. Dental laboratory materials were used to reproduce the periosteum and gum. The fabrication time per 3D model was about 2 hours and the cost per model was about $0.5. These models were used for lectures to resident dentists and periodontal surgery training, and their feedback was obtained. The resident's response to surgical training using these 3D models was generally positive. The use of FGF-2 represents a new direction in the treatment of periodontal disease. This being new, however, means that inexperienced periodontists require training in its application and how this will affect prognosis, as this will differ from that with more conventional techniques aimed at tissue regeneration. The low-cost 3D model presented in this report can be a valuable tool to help accomplish this in teaching inexperienced dentists, such as resident dentists.

Reproduction of modified Blumgart pancreaticojejunostomy in a robotic environment: a simple clipless technique.

BACKGROUND: Although modified Blumgart anastomosis (MBA) in robotic pancreaticoduodenectomy has been accepted as a simple and safe procedure that provides non-inferior surgical outcomes compared to open MBA, the details of the standardization of robotic MBAs have never been established. In this report, we detail the technical tips to reproduce MBA in the robotic environment. MATERIALS AND METHODS: From January to December in 2021, 16 patients underwent our novel robotic MBA technique, which included clipless Blumgart suture and duct-to-mucosa anastomosis. To simplify the manipulation of sutures in robotic environment, short double-armed sutures in 15 cm length were created and used for Blumgart suture. Duct-to-mucosa anastomosis were done by 5-0 monofilament of 6 cm length. These tips enabled clipless anastomosis and minimized the burden of the patient-side assistant. Surgical and short-term outcomes were compared between patients with robotic MBA (Robo group) and those who underwent open MBA during 2021 (32 patients, Open group). RESULTS: The median operation time was significantly longer in the Robo group than in the Open group (551 vs. 485.5 min, P = 0.0027). Estimated blood loss was significantly lower in the Robo group than in the open group (95 vs. 355 mL, P < 0.0002). The median duration of clipless MBA in the Robo group was 56 (46-68) min. The incidence of POPF (grade B or C) was not significantly different among the groups (19% vs. 22%, P = 0.71). The mean length of hospital stay was significantly shorter in the Robo group than in the Open group (18 vs. 24 days, P = 0.019). CONCLUSION: Clipless MBA in a robotic environment was safely performed with acceptable short-term outcomes and can be proposed as a standard technique for robotic pancreatojejunostomy.

KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer.

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62-1.75] and 1.05 [95% CI, 0.60-1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13-1.42; ptrend <0.001) and 1.31 (95% CI, 1.16-1.48; ptrend <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients.

Laparoscopic Radical Antegrade Modular Pancreatosplenectomy with Anterocranial Splenic Artery-First Approach for Left-Sided Resectable Pancreatic Cancer (with Videos).

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (Lap-RAMPS) for left-sided pancreatic cancer remains a technically challenging procedure. How to approach the splenic artery in laparoscopic surgery has not been discussed in adequate detail, and the implications of an artery-first approach in left-sided pancreatic cancer remain unclear. PATIENTS AND METHODS: Forty-five consecutive patients with left-sided resectable pancreatic cancer underwent Lap-RAMPS between July 2018 and September 2020. They were divided according to whether Lap-RAMPS was performed using an anterocranial splenic artery-first (ASF) approach (ASF group, n = 23) or via another approach (non-ASF group, n = 22). Clinical, pathological, and short-term outcomes were reviewed and compared between the groups. RESULTS: The ASF approach was performed safely in all patients with resectable left-sided pancreatic cancer, and none required conversion to laparotomy. The ASF group had better outcomes in terms of conspicuous bleeding from the spleen during splenic mobilization (P = 0.016) and blood pooling during posterior dissection (P = 0.035). Consequently, blood loss was significantly less and operation time was significantly shorter in the ASF group than in the non-ASF group. There was no significant between-group difference in other short-term outcomes, including mortality, length of hospital stay, or Clavien-Dindo classification. CONCLUSIONS: The ASF approach was safe when performed for resectable left-sided pancreatic cancer and may help to prevent congestion of the pancreas and lessen intraoperative blood loss.

Conversion surgery for recurrent hepatic angiosarcoma after systemic chemotherapy with paclitaxel.

A 67-year-old man presented with hemorrhagic shock due to the rupture of hepatic tumor and underwent emergency partial resection of the right liver. Pathological examination revealed hepatic angiosarcoma with involvement in its surgical margin. Six months after the operation, disease recurrence was detected, and he was referred to our hospital for second opinion. CT revealed tumors at the liver cut surface and left lateral segment. The tumor at the liver cut surface abutted to the common bile duct and the portal vein. The tumor was deemed unresectable, and systemic chemotherapy with 4 courses of weekly paclitaxel was given with excellent response. Then, we performed partial liver resection of S4 and S1 with remnant right liver and middle hepatic vein, and wedge resection for the metastatic lesion of segment 3 as a conversion surgery. He developed a grade B bile leakage postoperatively and was discharged on postoperative day 28. He remained disease free for 8 months after the operation.

A novel classification of portal venous tumor invasion to predict residual tumor status after surgery in patients with pancreatic neuroendocrine neoplasms.

PURPOSE: To elucidate whether portal venous tumor invasion (PVTI) is a prognostic factor for patients with pancreatic neuroendocrine neoplasms (Pan-NENs). METHODS: From 2002 to 2019, 240 patients with Pan-NEN were included to examine prognostic factors. PVTI based on computed tomography (CT) images are classified into four types: no PVTI (Vp0/1), PVTI not invading the superior mesenteric vein (Vp2), PVTI invading the superior mesenteric vein or portal vein (Vp3), and PVTI invading the portal bifurcation (Vp4). RESULTS: Simultaneous liver metastases (SLM) determined the overall survival (OS) in 240 patients. The 5-year OS rates with and without SLM were 46% and 92%, respectively (P < 0.001). PVTIs were observed in 56 of the 240 patients (23%). Among such patients, 39, 11, and 6 had Vp2, Vp3, and Vp4, respectively. The 5-year OS rates with and without PVTI were 62% and 82%, respectively (P < 0.001). Severity of PVTI did not decide PFS and OS after R0/1 resection. There was significant difference in the prognoses between Vp0/1 and Vp2-4. In 161 patients without SLM, 21 had PVTI (13%). According to a multivariate analysis, PVTI and Ki-67 index were independent prognostic factors for progression-free survival (PFS) in patients without SLM. The 5-year PFS rates with and without PVTI were 18% and 77%, respectively (P < 0.001). The 5-year OS rates with and without PVTI were 76% and 95%, respectively (P = 0.02). PVTI was associated with tumor functionality, high serum NSE, and high Ki-67 index. CONCLUSIONS: PVTI may be a predictor for postoperative recurrence.