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.

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.

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.

Selection criteria for minimally invasive resection of intrahepatic cholangiocarcinoma-a word of caution: a propensity score matched analysis using the national cancer database.

BACKGROUND: While minimally invasive liver resection (MILR) vs. open approach (OLR) has been shown to be safe, the perioperative and oncologic safety for intrahepatic cholangiocarcinoma (ICC) specifically, necessitating often complex hepatectomy and extended lymphadenectomy, remains ill-defined. METHODS: The National Cancer Database was queried for patients with ICC undergoing liver resection from 2010 to 2016. After 1:1 Propensity Score Matching (PSM), Kruskal-Wallis and χ2 tests were applied to compare short-term outcomes. Kaplan-Meier survival analyses and Cox multivariable regression were performed. RESULTS: 988 patients met inclusion criteria: 140 (14.2%) MILR and 848 (85.8%) OLR resulting in 115 patients MILR and OLR after 1:1 PSM with c-index of 0.733. MILR had lower unplanned 30-day readmission [OR 0.075, P = 0.014] and positive margin rates [OR 0.361, P = 0.011] and shorter hospital length of stay (LOS) [OR 0.941, P = 0.026], but worse lymph node yield [1.52 vs 2.07, P = 0.001]. No difference was found for 30/90-day mortality. Moreover, multivariate analysis revealed that MILR was associated with poorer overall survival compared to OLR [HR 2.454, P = 0.001]. Subgroup analysis revealed that survival differences from approach were dependent on major hepatectomy, tumor size > 4 cm, or negative margins. CONCLUSION: MILR vs. OLR is associated with worse lymphadenectomy and survival in patients with ICC greater than 4 cm requiring major hepatectomy. Hence, MILR major hepatectomy for ICC should only be approached selectively and if surgeons are able to perform an appropriate lymphadenectomy.

Failure to Cure Patients with Colorectal Liver Metastases: The Impact of the Liver Surgeon.

BACKGROUND: Lack of a liver surgeon (LS) may lead to failure to cure in patients with possibly resectable colorectal liver metastases (CRLM). This study aims to quantify the failure-to-cure rate due to noninclusion of an LS. PATIENTS AND METHODS: All patients who underwent chemotherapy with palliative intent for CRLM at a community oncology network between 2010 and 2018 were identified from a prospectively maintained cancer registry. Two LS blinded to patient management and outcome reviewed pretreatment imaging and assigned each scan a newly developed resectability score. Nominal group technique and independent scores were combined to determine probability of curative-intent resection. Interobserver agreement was calculated using κ testing. RESULTS: This study included 72 palliative CRLM patients. Demographic factors were: 44 (59%) male, median age 68 years (range 36-94 years), 23 (32%) rectal primary, 24 (33%) receiving oxaliplatin-based chemotherapy. Of the 72 patients with CRLM, 6 had left-sided metastases only. The median number of CRLM was 6 (1-8). Agreement on resectability was achieved in 32 (44%) patients for the entire cohort and 17 (54%) in patients without extrahepatic disease. A lower median number of CRLM was found in the group considered to be resectable by the two LS (2 versus 8; p = 0.001). Substantial agreement was found between liver surgeons in the group of patients without extrahepatic disease (κ = 0.9043). CONCLUSIONS: Over 44% of patients who were assigned palliative chemotherapy at tumor boards without an LS were considered potentially resectable upon independent LS review.

Laparoscopic Pancreatic Head Preserving Total Duodenectomy: The Parenchymal Sparing Alternative to a Whipple.

BACKGROUND: When endoscopic options fail, laparoscopic pancreatic head-preserving duodenectomy (LPHPD) for benign duodenal lesions is a parenchymal sparing and safe alternative to a pancreaticoduodenectomy.1-3 LPHPD may be the optimal "amount" of surgery, because such lesions are at risk for undertreatment (partial endoscopic resection associated with recurrence) or overtreatment (Whipple associated with morbidity and loss of pancreatic parenchyma).4,5 PATIENT: A 80-year-old, healthy female patient was diagnosed endoscopically with two, flat, symptomatic adenomas (7-cm D2; 2-cm D3). She had no family history of polyposis. Germline testing, tumor markers, and colonoscopy did not show any abnormality. TECHNIQUE: With the patient in French position, a wide laparoscopic Kocherization was performed past IVC and aorta. Following prepyloric gastric transection, the entire duodenum was carefully dissected off the pancreas. After transection of the proximal jejunum, the reconstruction begins. A two-layer, duct-to-mucosa, ampullary-jejunal anastomosis and a type II Billroth gastrojejunostomy were performed. CONCLUSIONS: LPHPD avoids under- or overtreatment of benign duodenal lesions unamenable to an endoscopic approach. If the stepwise approach described in this video is followed, LPHPD represents a safe and parenchymal-sparing alternative to pancreaticoduodenectomy for benign duodenal lesions with reduced morbidity.

Does a Laparoscopic Approach to Distal Pancreatectomy for Cancer Contribute to Optimal Adjuvant Chemotherapy Utilization?

BACKGROUND: Although laparoscopic distal pancreatectomy (LDP) versus open approaches (ODP) for pancreatic adenocarcinoma (PDAC) is associated with reduced morbidity, its impact on optimal adjuvant chemotherapy (AC) utilization remains unclear. Furthermore, it is uncertain whether oncologic resection quality markers are equivalent between approaches. METHODS: The National Cancer Database (NCDB) was queried between 2010 and 2016 for PDAC patients undergoing DP. Effect of LDP vs ODP and institutional case volumes on margin status, hospital stay, 30-day and 90-day mortality, administration of and delay to AC, and 30-day unplanned readmission were analyzed using binary and linear logistic regression. Cox multivariable regression was used to correct for confounders. RESULTS: The search yielded 3411 patients; 996 (29.2%) had LDP and 2415 (70.8%) had ODP. ODP had higher odds of readmission [odds ratio (OR) 1.681, p = 0.01] and longer hospital stay [ß 1.745, p = 0.004]. No difference was found for 30-day mortality [OR 1.689, p = 0.303], 90-day mortality [OR 1.936, p = 0.207], and overall survival [HR 1.231, p = 0.057]. The highest-volume centers had improved odds of AC [OR 1.275, p = 0.027] regardless of approach. LDP conferred lower margin positivity [OR 0.581, p = 0.005], increased AC use [3rd quartile: OR 1.844, p = 0.026; 4th quartile; OR 2.144, p = 0.045], and fewer AC delays [4th quartile: OR 0.786, p = 0.045] in higher-volume centers. CONCLUSIONS: In selected patients, LDP offers an oncologically safe alternative to ODP for PDAC independent of institutional volume. However, additional oncologic benefit due to optimal AC utilization and lower positive margin rates in higher volume centers suggests that LDP by experienced teams can achieve best possible cancer outcomes.

Western population-based study of oncologic surgical quality and outcomes of laparoscopic versus open gastrectomy for gastric adenocarcinoma.

BACKGROUND: While studies have reported improved morbidity of laparoscopic (LG) compared with open gastrectomy (OG), it remains unclear whether comparable oncologic outcomes can be achieved. This study aims at comparing not only short-term outcomes, including 30- and 90-day mortality, but also survival of LG vs OG. METHODS: The National Cancer Database was searched for adult patients with histologically proven gastric cancer and complete information regarding M0 disease, tumor size, differentiation grade, T stage, nodal status, comorbidities, type of hospital, hospital stay, type of surgery, oncological treatment and survival data were included. Logistic regression analyses were performed to analyze margin status, 30- and 90-day mortality, and 30-day re-admission rate. Linear regression was performed for length of hospital stay and lymph node yield. Kaplan-Meier survival analyses were performed to evaluate median survival. Cox multivariable regression models were created to correct for confounders and identify factors affecting survival. RESULTS: A query of the National Cancer Database identified 13,538 patients with complete dataset. A significant regression equation favoring LG for lymph node yield, hospital stay, and unplanned re-admission rate was identified. There was no significant effect of surgical approach on R1 margin rate, 30-day mortality, or 90-day mortality. Median survival was comparable between LG and OG (44.8 vs 40.2 months, p = 0.804). CONCLUSION: LG offers a safe surgical approach to gastric cancer with shorter hospital stay and lower re-admission rates than OG, and also similar and sometimes improved operative oncologic quality parameters (margin, lymph node yield). More importantly, this Western series demonstrates that equivalent long-term outcomes of LG vs. OG are being achieved.

Delayed presentation of doxorubicin extravasation into pleural space: Case report and review of literature.

INTRODUCTION: Intrathoracic extravasation of anthracyclines is a dangerous and very rare complication of chemotherapy administration. While management of extravasation into soft tissues has been established, the data on treatment of mediastinal and intrapleural anthracycline extravasation is limited. CASE REPORT: We present a case of a 52-year-old woman with intrapleural doxorubicin extravasation who presented to the hospital 24-hrs after chemotherapy infusion with chest pain and shortness of breath. MANAGEMENT & OUTCOME: The patient underwent urgent surgical intervention and received IV dexrazoxane 36-hrs after the event. Her pain improved, but she continued to have chest soreness and pleural effusion at the site of extravasation even 3 months later. DISCUSSION: We conducted review of literature using Medline/PubMed and Google Scholar databases and identified 7 cases of intrapleural and mediastinal anthracycline extravasation. No data is currently available regarding the outcome of delayed management of intrapleural anthracycline extravasation with dexrazoxane. Prevention and confirmation of adequate port catheter placement is the most important step to avoid such cases. Catheter misplacement should be suspected in any patient presenting with post procedural chest pain and should trigger a thorough evaluation prior to any chemotherapy administration.

Laparoscopic pancreatectomy for cancer in high volume centers is associated with an increased use and fewer delays of adjuvant chemotherapy.

BACKGROUND: This study aimed to investigate the relationship between hospital case volume, surgical approach and AC-use in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients were divided into quartiles by institutional pancreatectomy case volume, resection type (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or total pancreatectomy [TP]) and surgical approach (laparoscopic vs. open). The rates and contributing factors of AC administration and delay >90 days were compared among volume quartiles and surgical approaches. RESULTS: This study identified 23,494 patients who had undergone pancreatectomy for PDAC between 2010 and 2016 and met inclusion criteria. After correcting for confounders, compared to low volume hospitals patients at high-case-volume hospitals had the highest rates of AC administration after PD and DP. Moreover, compared to open surgery for all resection types, laparoscopic surgery was associated with a higher rate of AC use at high and highest-case-volume hospitals and less delay to chemotherapy at high-volume hospitals. For DP, laparoscopic approach had a positive impact on AC delay >90-day at the highest volume institutions only. CONCLUSIONS: Laparoscopic surgery for pancreatic cancer leads to higher utilization and lower probability of delay of AC in high and highest volume hospitals.

Laparoscopic Segment 1 with Partial IVC Resection in Advanced Cirrhosis: How to Do It Safely.

BACKGROUND: Laparoscopic versus open hepatocellular carcinoma (HCC) resection reduces morbidity without a compromise in oncologic safety.1-4 Moreover, in the subgroup of cirrhotic patients, a decreased risk of prolonged postoperative ascites and liver decompensation has been reported.5-7 METHODS: A 54-year-old homeless, deaf male with chronic alcoholism, hepatitis C, and advanced cirrhosis was referred with a caudate tumor from a critical access hospital. Imaging showed a 3.6-cm HCC in the caudate lobe compressing the inferior vena cava (IVC). With the patient in reversed, modified French position, the liver was mobilized, and the hepatocaval space dissected. Portal and short hepatic vein branches were individually controlled, and the caudate lobe was dissected off the IVC. At the superior portion of the Spiegel process, the tumor was inseparable from the IVC, necessitating en bloc segment 1 with partial IVC resection. The IVC was reconstructed laparoscopically following a preplanned approach. The pathology report confirmed R0 resection of a moderately differentiated hepatocellular carcinoma without microvascular or perineural invasion (pT1bN0M0). CONCLUSION: Laparoscopic caudate lobectomy for cirrhotic patients with partial IVC resection is technically demanding. It therefore requires a strategic and preplanned approach with dedicated instrumentation and laparoscopic skills available. Although the caudal view along the axis of the IVC facilitates dissection, a laparoscopic approach necessitates particular attention to central venous pressure management (intravenous fluid and respiratory tidal volume), meticulous control of portal and short hepatic vein branches, and availability of specialty laparoscopic instrumentation to ensure procedural safety.

Hyperammonemic Encephalopathy Associated With Fibrolamellar Hepatocellular Carcinoma: Case Report, Literature Review, and Proposed Treatment Algorithm.

UNLABELLED: We report a case of a 31-year-old man with metastatic fibrolamellar hepatocellular carcinoma (FLHCC) treated with gemcitabine and oxaliplatin complicated by hyperammonemic encephalopathy biochemically consistent with acquired ornithine transcarbamylase deficiency. Awareness of FLHCC-associated hyperammonemic encephalopathy and a pathophysiology-based management approach can optimize patient outcome and prevent serious complications. A discussion of the management, literature review, and proposed treatment algorithm of this rare metabolic complication are presented. IMPLICATIONS FOR PRACTICE: Pathophysiology-guided management of cancer-associated hyperammonemic encephalopathy can improve patient outcome and prevent life-threatening complications. Community and academic oncologists should be aware of this serious metabolic complication of cancer and be familiar with its management.

Outcome of patients with positive heparin-platelet factor-4 antibodies: A retrospective multi-institutional observational study.

Studies show increased mortality with positive heparin-platelet factor-4 (H-PF4) antibodies, especially in hemodialysis patients. We aimed to compare mortality and thrombosis in hospitalized patients with positive, equivocal and negative H-PF4 antibody results. Information was collected on these patients using a multi-institutional retrospective electronic medical record review. Patients tested for H-PF4 antibodies by commercial ELISA during the years 2006 to 2010 were identified. We compared 30-day, 90-day and 1-year mortality in patients with negative, equivocal and positive H-PF4 test and evaluated the relationship between H-PF4 status and rate of thrombosis. Four hundred and seventeen patients had ELISA testing for H-PF4 antibodies. Forty-four patients had equivocal (optical density value 0.4-0.9) and 21 had positive (value 1) H-PF4 antibody test. There were no statistically significant differences in mortality between patients with negative, equivocal and positive results at all three time points (p = 0.22, 0.27 and 0.38, respectively) even after excluding patients with thrombosis (p = 0.22, 0.24 and 0.31, respectively). Age and Charlson score were associated with increased 30-day, 90-day and 1 year mortality. Odds ratio of having thrombosis was 23.1 for positive vs. equivocal results (p < 0.001); however, there was no statistically significant difference between equivocal vs. negative results (p = 0.22). Our results revealed no association between H-PF4 status and mortality, as well as no difference in 1-year survival between the positive and negative groups.

5α-reductase type 3 enzyme in benign and malignant prostate.

BACKGROUND: Currently available 5α-reductase inhibitors are not completely effective for treatment of benign prostate enlargement, prevention of prostate cancer (CaP), or treatment of advanced castration-recurrent (CR) CaP. We tested the hypothesis that a novel 5α-reductase, 5α-reductase-3, contributes to residual androgen metabolism, especially in CR-CaP. METHODS: A new protein with potential 5α-reducing activity was expressed in CHO-K1 cellsandTOP10 E. coli for characterization. Protein lysates and total mRNA were isolated from preclinical and clinical tissues. Androgen metabolism was assessed using androgen precursors and thin layer chromatography or liquid chromatography tandem mass spectrometry. RESULTS: The relative mRNA expression for the three 5α-reductase enzymes in clinical samples of CR-CaP was 5α-reductase-3 ≫ 5α-reductase-1> 5α-reductase-2. Recombinant 5α-reductase-3 protein incubations converted testosterone, 4-androstene-3,17-dione (androstenedione) and 4-pregnene-3,20-dione (progesterone) to dihydrotestosterone, 5α-androstan-3,17-dione, and 5α-pregnan-3,20-dione, respectively. 5α-Reduced androgen metabolites were measurable in lysates from androgen-stimulated (AS) CWR22 and CR-CWR22 tumors and clinical specimens of AS-CaP and CR-CaP pre-incubated with dutasteride (a bi-specific inhibitor of 5α-reductase-1 and 2). CONCLUSION: Human prostate tissues contain a third 5α-reductase that was inhibited poorly by dutasteride at high androgen substrate concentration in vitro, and it may promote DHT formation in vivo, through alternative androgen metabolism pathways when testosterone levels are low.

Structure and dynamics of adeno-associated virus serotype 1 VP1-unique N-terminal domain and its role in capsid trafficking.

The importance of the phospholipase A2 domain located within the unique N terminus of the capsid viral protein VP1 (VP1u) in parvovirus infection has been reported. This study used computational methods to characterize the VP1 sequence for adeno-associated virus (AAV) serotypes 1 to 12 and circular dichroism and electron microscopy to monitor conformational changes in the AAV1 capsid induced by temperature and the pHs encountered during trafficking through the endocytic pathway. Circular dichroism was also used to monitor conformational changes in AAV6 capsids assembled from VP2 and VP3 or VP1, VP2, and VP3 at pH 7.5. VP1u was predicted (computationally) and confirmed (in solution) to be structurally ordered. This VP domain was observed to undergo a reversible pH-induced unfolding/refolding process, a loss/gain of α-helical structure, which did not disrupt the capsid integrity and is likely facilitated by its difference in isoelectric point compared to the other VP sequences assembling the capsid. This study is the first to physically document conformational changes in the VP1u region that likely facilitate its externalization from the capsid interior during infection and establishes the order of events in the escape of the AAV capsid from the endosome en route to the nucleus.

Capsid antibodies to different adeno-associated virus serotypes bind common regions.

Interactions between viruses and the host antibody immune response are critical in the development and control of disease, and antibodies are also known to interfere with the efficacy of viral vector-based gene delivery. The adeno-associated viruses (AAVs) being developed as vectors for corrective human gene delivery have shown promise in clinical trials, but preexisting antibodies are detrimental to successful outcomes. However, the antigenic epitopes on AAV capsids remain poorly characterized. Cryo-electron microscopy and three-dimensional image reconstruction were used to define the locations of epitopes to which monoclonal fragment antibodies (Fabs) against AAV1, AAV2, AAV5, and AAV6 bind. Pseudoatomic modeling showed that, in each serotype, Fabs bound to a limited number of sites near the protrusions surrounding the 3-fold axes of the T=1 icosahedral capsids. For the closely related AAV1 and AAV6, a common Fab exhibited substoichiometric binding, with one Fab bound, on average, between two of the three protrusions as a consequence of steric crowding. The other AAV Fabs saturated the capsid and bound to the walls of all 60 protrusions, with the footprint for the AAV5 antibody extending toward the 5-fold axis. The angle of incidence for each bound Fab on the AAVs varied and resulted in significant differences in how much of each viral capsid surface was occluded beyond the Fab footprints. The AAV-antibody interactions showed a common set of footprints that overlapped some known receptor-binding sites and transduction determinants, thus suggesting potential mechanisms for virus neutralization by the antibodies.

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.