Improved outcomes for borderline resectable adenocarcinoma of the pancreas after neoadjuvant chemotherapy in a community cancer center.

BACKGROUND: Borderline resectable adenocarcinoma of the pancreas involves the major vascular structures adjacent to the pancreas and has traditionally led to poor resection rates and survival. Newer chemotherapy regimens have demonstrated improved response and resection rates. We performed a retrospective review of borderline resectable pancreatic cancers who presented to a community cancer program to determine the effect of neoadjuvant chemotherapy to improve resection rates and overall survival. METHODS: Records of all patients diagnosed with adenocarcinoma of the pancreas from January 1, 2015 to December 31, 2019 were reviewed to determine stage at presentation, resectablility status, treatment methods, surgical resection and survival. Borderline resectable status was determined by preoperative imaging in agreement with published criteria from the National Comprehensive Cancer Network (NCCN) Guidelines 2.2021. Data was collected and analyzed by standard t-test. This study was approved by the institution's IRB. RESULTS: During this time period 322 patients were diagnosed with ductal adenocarcinoma of the pancreas of which 151 (47%) were unresectable, 31 (10%) were locally advanced, 70 (22%) were borderline resectable, and 69 (21%) were resectable at the time of presentation. 36 (51%) of the borderline resectable patients underwent neoadjuvant chemotherapy at our institution with either FOLFIRINOX or gemcitibine/nab-Paclitaxel regimens and served as the basis for this analysis. After neoadjuvant chemotherapy 24 (68%) of the borderline-resectable patients were deemed suitable for surgical exploration. At exploration, 15 (64%) were resected with 9 (60%) achieving margin-free resection on final pathology. The overall survival of those that underwent resection was increased by 19.6 months compared to those that did not undergo surgery (35.4 versus 15.8 mos, p < 0.01). Overall morbidity after resection was 46% (33% class 1 or 2, 13% class 3) with 0% mortality at 90 days. CONCLUSIONS: Use of neoadjuvant chemotherapy for borderline resectable adenocarcinoma of the pancreas results in improved resection rates and overall survival in resected patients. This management strategy for ductal adenocarcinoma of the pancreas is safe and feasible in a community-based cancer program.

Current Trends in Surgical Procedures Performed in Rural General Surgery Practice.

BACKGROUND: The procedures that rural general surgeons perform may be changing. It is important to recognize the trends and practices of the current rural general surgeon in efforts to better prepare general surgeons who desire to enter a practice in a rural environment. The aim of this review is to detail the recent operative case volumes of 6 rural locations in the upper Midwest where general surgery is practiced. METHODS: The Enterprise Data and Analytics department of Sanford Health compiled all surgical procedures performed within the Sanford Health System between January 1, 2013 and August 31, 2018. Procedures performed by a total of 58 general surgeons in locations of under 50 000 people are included in this review. RESULTS: From January 1, 2013 to August 31, 2018, 38 958 surgical procedures were performed in rural locations. Endoscopic procedures made up 61.6% of a rural general surgeon's practice. Cholecystectomy (6.3%), hernia repair (6.3%), and appendectomy (3.7%) were the principle nonendoscopic procedures performed by rural surgeons, comprising 16.3% of the case volume. Added together, endoscopy, cholecystectomy, hernia repair, and appendectomy made up 77.9% of the rural general surgeon's caseload. Vascular procedures (2.5%), breast procedures (1.8%), obstetrics (0.4%), and urology procedures (0.2%) are also included in this review. CONCLUSIONS: Rural general surgeons are vital to the surgical workforce in the United States. Recognizing a trend that rural general surgeons perform less subspecialty procedures and more endoscopic procedures will provide direction for those interested in pursuing a career in rural general surgery.

Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance]).

AIM: report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. METHODS: In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). RESULTS: Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). CONCLUSIONS: Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

Metastasectomy and surgical resection of the primary tumor in patients with stage IV breast cancer: time for a second look?

Patients with metastatic or stage IV breast cancer have limited therapeutic options, and the mainstay of treatment remains systemic chemotherapy. Traditionally, the role of surgery has been confined to strict palliation. Improvements in the efficacy of chemotherapeutic regimens, coupled with the use of hormonal and targeted therapy, have resulted in an expansion of surgical resection beyond simple palliation. Several single-institution studies have reported improved survival and even long-term cures after surgical resection for oligometastatic stage IV breast cancer. Similarly, provocative new data suggest that removal of the primary tumor in some patients may confer a survival advantage. The aim of this review is to summarize studies in the medical literature pertaining to the use of surgical resection in patients with stage IV breast cancer. We believe there is enough evidence to challenge conventional thinking about the role of surgery in stage IV breast cancer and to consider a new multimodality treatment paradigm to optimize patient outcomes. It is time to conduct a carefully designed randomized trial to see whether surgery in stage IV breast cancer does indeed warrant a second look.

Advanced Technology and the Rural Surgeon.

Advanced technology has resulted in major changes in surgery and medicine over the past three decades. There are many barriers to the adoption of advanced technologies, which can be more prevalent in rural hospitals and surgical practices. Despite barriers to implementation of new technologies in rural communities, many rural hospitals have endorsed and invested in these technologies for the benefit of the hospital and community. The rural surgeon is often the driving force in evaluating and deciding on new technologies for their surgical program. This article discusses advantages, challenges, and limitations in the use of advanced technologies in rural locations.

Combined treatment of dendritoma vaccine and low-dose interleukin-2 in stage IV renal cell carcinoma patients induced clinical response: A pilot study.

Vaccination using dendritic/tumor cell hybrids represents a novel and promising cancer immunotherapy. We have developed a technology that can instantly purify the hybrids (dendritomas) from the fusion mixture of dendritic cells (DCs) and tumor cells. Our animal studies and a phase I study of stage IV melanoma patients demonstrated that dendritoma vaccination could be conducted without major toxicity and induced tumor cell-specific immunological and clinical responses. In this pilot study, ten stage IV renal cell carcinoma patients were studied. Dendritomas were made from autologous DCs and tumor cells and administered by subcutaneous injection. After initial vaccination, three escalating doses of IL-2 (3, 6, and 9 million units each) were followed within five days. This treatment regimen was tolerated well without severe adverse events directly related to the dendritoma vaccine. Most adverse events were related to IL-2 administration or pre-existing disease. Patient-specific immune responses were evaluated by flow cytometric measurement of interferon-gamma-producing T-cells before and after vaccination in response to stimulation with tumor antigens. Nine out of nine patients eligible for the analysis showed an increase of IFN-gamma-expressing CD4+ T cells after vaccination(s); while five out of eight patients eligible for the analysis showed an increase of IFN-gamma-expressing CD8+ T cells. Clinical responses were documented in 40% of the patients, three with stabilization of disease and one with a partial response documented by a reduction in tumor size. This pilot study demonstrated that dendritoma vaccines could be administered safely to patients with metastatic renal cell carcinoma, while producing both clinical and immunologic evidence of response.

Basic and tumor immunology: a review.

The immune system is one of the most important means by which more complex animals protect themselves from external threats. There are two immune systems: the innate and the adaptive. The innate is the most basic and has existed for the longest time; the adaptive immune system is a more recent evolutionary development. The immune system plays a critical role in surveillance and prevention of malignancy. It is only when malignant cells develop mechanisms to escape the immune system that they become clinically significant tumors. Our knowledge of the immune system has grown enormously. We have begun to understand not only the mechanisms by which it protects us but also the ways in which it can inflict injury on the body. We are also learning about how it communicates with the environment and how its various components interact within the body. With this information, we are learning how to manipulate it to our greater benefit.

The surgeon's role in immunotherapy.

Immunotherapy in the multidisciplinary care of the cancer patient will play an increasingly important role in cancer therapy for solid tumors. Strategies to optimize surgical management for an effective immune response against tumors should be acknowledged and promoted by the surgical community. Immunotherapy can serve as a beneficial adjunct to surgical excision for high-risk and recurrent tumors, with the attraction of decreased toxicity and disability over current adjuvant treatment methods. It is important that surgeons recognize immunotherapy's potential and play an active role in developing immunotherapy treatment regimens, for without surgical involvement many of these therapies may never come to fruition. This article reviews the key roles that surgeons play in immunotherapy treatment and research.

Dendritoma vaccination combined with low dose interleukin-2 in metastatic melanoma patients induced immunological and clinical responses.

A pilot clinical trial using dendritomas, purified hybrids from the fusion of dendritic/tumor cells combined with a low dose of IL-2, in metastatic melanoma patients was conducted in order to determine its safety and potential immunological and clinical responses. Ten metastatic melanoma patients were enrolled into this study. Dendritoma vaccines were created by fusing dendritic cells stained with green fluorescent dye with irradiated autologous tumor cells stained with red fluorescent dye and purifying the hybrids using immediate fluorescent-activated cell sorting. Initial vaccine was given subcutaneously and followed by IL-2 in serially elevated doses from 3-9 million units/m2 for 5 days. Repeated vaccinations were administered without IL-2, at 3-month intervals for a maximum of 5 times. Immune reactions were measured by the increase of interferon-gamma (IFN-gamma) expressing T cells. Vaccine doses ranged from 250,000 to 1,000,000 dendritomas. There was no grade 2 or higher toxicity directly attributable to the vaccine. All patients experienced toxicity due to IL-2 administration (9-grade 2, 3-grade 3, 1-grade 4). Eight of nine evaluable patients demonstrated immunologic reactions by increased IFN-gamma expressing T cells. One patient developed partial response at 12 weeks after the first vaccine. Nine months later, this patient achieved a complete response. In addition, two patients had stable disease for 9 and 4 months, respectively; one patient had a mixed response. Our findings demonstrated that dendritoma vaccines with a low dose of IL-2 can be safely administered to patients with metastatic melanoma and induce immunological and clinical responses.

Cerebral protection during carotid endarterectomy.

BACKGROUND: Perioperative stroke rates with carotid endarterectomy are 3.4% for asymptomatic and 5.2% for symptomatic patients. Several methods are used to limit perioperative stroke. METHODS: A retrospective chart review of consecutive carotid endarterectomies from January 1, 2000 to February, 28, 2003, was performed. Data were collected on patient demographics, operative procedure, intraoperative monitoring, and outcome. Comparative analysis of intraoperative monitoring and outcome was performed. RESULTS: Two hundred twenty-nine patients underwent 251 carotid endarterectomies. In 196 procedures decision to shunt was based on intraoperative monitoring, 129 by electroencephalogram (EEG), and 67 by stump pressures. Sixteen neurologic events occurred perioperatively, one transient ischemic attack and 15 strokes. The EEG group had 12 strokes, with a 38% event rate in procedures with EEG changes without shunting. The stump pressure group had one stroke. Stroke rate for intraoperative EEG monitoring was elevated (P = 0.02). CONCLUSIONS: Intraoperative EEG based decision to shunt may not be as effective as other methods for prevention of perioperative neurologic events. When EEG changes occur, shunting is necessary.

Rationale for hyperthermia with intraoperative intraperitoneal chemotherapy agents.

Hyperthermia is selectively cytotoxic for malignant cells due to inhibition of oxidative metabolism causing lower pH in the microenvironment of the malignant cells and tumor. The increased acidity increases lysosymal activity and subsequent cell death. Hyperthermia alone as a primary treatment modality for malignancy has largely been abandoned due to high morbidity and mortality and high recurrence rates. Advances in administration and monitoring of hyperthermia, especially for regional applications, has allowed for the use of hyperthemia in conjunction with other modalities of antineoplastic therapy. Hyperthermia has been shown to potentiate chemotherapy and radiation by several different mechanisms. HIIC uses the advantages of hyperthermia in conjunction with chemotherapy for the management of peritoneal carcinomatosis. Several different chemotherapy agents have been shown to have improved therapeutic index and efficacy when used with hyperthermia in the management of peritoneal carcinomatosis.

Current management of common bile duct stones in a teaching community hospital.

The advent of laparoscopic cholecystectomy (LC) has complicated management of common bile duct (CBD) stones. While LC is routine, laparoscopic CBD exploration (LCBDE) is not, and an algorithm to manage suspected choledocholithiasis has not been uniformly accepted. We evaluated current management of choledocholithiasis. Patients suspected of having CBD stones over a 2-year period were evaluated, and 42 studies in the literature were reviewed. Thirty-two patients were identified. Fourteen patients (44%) had LC with intraoperative cholangiogram (IOC) with no preoperative studies. IOC revealed CBD stones in nine (64%). Seven had CBD exploration (CBDE) at cholecystectomy, and two had postoperative endoscopic retrograde cholangiopancreatography (ERCP). CBDE was successful in five cases, and ERCP was successful in one. Eighteen patients (56%) underwent preoperative ERCP. Five (28%) had no CBD stones. ERCP removed stones in nine patients, and four had open CBDE after failed ERCP. Current literature supports LC with IOC without any preoperative studies. Laparoscopic CBDE is highly successful but depends on surgeon experience. Removing CBD stones with ERCP is also very successful but is associated with increased cost, hospital stay, and complications. We conclude that LC with IOC should be performed without preoperative ERCP when choledocholithiasis is suspected. If found, stones should be removed laparoscopically if possible.

Effect of alcohol on surgical dexterity after a night of moderate alcohol intake.

BACKGROUND: Alcohol misuse is commonplace among health professionals. The effects of alcohol on cognition and dexterity have been shown up to 14 hours after alcohol intake. The aerospace industry has restrictions on alcohol intake, and there is pressure for the health care industry to do the same. Few studies have addressed the lingering impact alcohol has on surgical performance, and none have measured surgical dexterity using well-established Fundamentals of Laparoscopic Surgery benchmarks. METHODS: Twenty-seven surgeons participated in this study: 11 attending surgeons, 2 fellows, and 14 resident surgeons. Three Fundamentals of Laparoscopic Surgery tasks measured surgical dexterity: peg transfer, pattern cutting, and intracorporeal suturing. Performance on these tasks was measured before alcohol intake and the morning after a night of social drinking. Alcohol levels were measured via breathalyzer 20 minutes after completion of drinking and the following morning before testing. Time and accuracy were compared. RESULTS: The mean blood alcohol level was .076 mg/100 mL blood. Times for peg transfer, pattern cutting, and intracorporeal suturing showed no differences. Accuracy in pattern cutting was not different, but accuracy for intracorporeal suturing was significantly worse the morning after alcohol intake. CONCLUSIONS: The morning after moderate alcohol intake, the time to complete Fundamentals of Laparoscopic Surgery tasks was unchanged, but accuracy was worse.

Are open abdominal procedures a thing of the past? An analysis of graduating general surgery residents' case logs from 2000 to 2011.

INTRODUCTION: Since the introduction of laparoscopic surgery for cholecystectomy in 1989, the growth of minimally invasive surgery (MIS) has increased significantly in the United States. There is a growing concern that the pendulum has now shifted too far toward MIS and that current general surgery residents' exposure to open abdominal procedures is lacking. OBJECTIVE: We sought to analyze trends in open vs MIS intra-abdominal procedures performed by residents graduating from US general surgery residency programs over the past twelve years. METHODS: We conducted a retrospective analysis of the data from the ACGME national resident case log reports for graduating US general surgery residents from 2000 to 2011. We analyzed the average number of cases per graduating chief resident for the following surgical procedures: appendectomy, inguinal/femoral hernia repair, gastrostomy, colectomy, antireflux procedures, and cholecystectomy. RESULTS: For all the procedures analyzed, except antireflux procedures, a statistically significant increase in the number of MIS cases was seen. The increases in MIS procedures were as follows: appendectomy, 8.5 to 46 (542%); inguinal/femoral hernia repair, 7.6 to 23.3 (265%); gastrostomy, 1.4 to 3 (114%); colectomy, 1.8 to 18.2 (1011%); and cholecystectomy, 84 to 105.7 (26%). The p value was set at <0.001 for all procedures. There has been a concomitant decrease in the number of open procedures. The numbers of open appendectomy decreased from 30.9 to 15.5 (p < 0.0001), open inguinal/femoral hernia repair from 52.1 to 48 (p = 0.0038), open gastrostomy from 7.7 to 4.9 (p = 0.0094), open colectomy from 48 to 40.7 (p < 0.0001), open cholecystectomy from 15.5 to 10.4 (p = 0.0005), and open antireflux procedures from 4.7 to 1.7 (p < 0.001). An analysis conducted over time reveals that the rates of increase in MIS procedures in 5 of the 6 categories continue to rise, whereas the rates of open appendectomy, open colectomy, and open antireflux procedures continue to decrease. However, the rates of decline of open hernia repairs and open gastrostomies seem to have plateaued. CONCLUSIONS: The performance of open procedures in general surgery residency has declined significantly in the past 12 years. The effect of the decline in open cases in surgical training and practice remains to be determined.

Current use and surgical efficacy of laparoscopic colectomy in colon cancer.

BACKGROUND: The Clinical Outcomes in Surgical Therapy trial demonstrated that laparoscopic colectomy (LC) was equivalent to open colectomy (OC) for 30-day mortality, time to recurrence, and overall survival in colon cancer (CC) patients. Current use of LC for CC is not well known. STUDY DESIGN: Surgical data were reviewed for all patients randomized into a national phase III clinical trial for adjuvant therapy in stage III CC (North Central Cancer Treatment Group trial N0147). Colon resections were grouped as open (traditional laparotomy) or laparoscopic, including laparoscopic; laparoscopic assisted; hand assisted; and laparoscopic converted to OC. Statistical methods included nonparametric methods, categorical analysis, and logistic regression modeling. RESULTS: A total of 3,393 evaluable patients were accrued between 2004 and 2009; 53% were male, median age was 58 years, 86% were white, and 70% had a body mass index >25 kg/m(2). Two thousand one hundred thirteen (62%) underwent OC. One thousand two hundred eighty (38%) were initiated as laparoscopic procedures, 25% (n = 322) were laparoscopic, 32% (n = 410) were laparoscopic assisted, 26% (n = 339) were hand assisted, and 16% (n = 209) were LC converted to OC. Significant predictors of LC (vs OC) in multivariate models were T stage (T1 or T2 vs T3 or T4; p = 0.0286), and absence of perforation, bowel obstruction, or adherence to surrounding organs (p < 0.01 each). Increasing rates of LC were observed over time, with LC eclipsing OC in 2009 (p < 0.0001). Surgical efficacy, measured by lymph node retrieval, was similar, with the mean number of lymph nodes retrieved higher in the LC group (20.6 vs 19.5 nodes; p = 0.0006). CONCLUSIONS: This study demonstrated a steadily increasing use of LC for the surgical treatment of CC between 2004 and 2009, with LC preferred by study completion. Surgical efficacy was similar in stage III CC patients.

Multi-institutional study of self-reported attitudes and behaviors of general surgery residents about ethical academic practices in test taking.

PURPOSE: Correlation exists between people who engage in academic dishonesty as students and unethical behavior once in practice. Previously, we assessed the attitudes of general surgery residents and ethical practices in test taking at a single institution. Most residents had not participated in activities they felt were unethical, yet what constituted unethical behavior was unclear. We sought to verify these results in a multi-institutional study. METHODS: A scenario-based survey describing potentially unethical activities related to the American Board of Surgery In-training Examination (ABSITE) was administered. Participants were asked about their knowledge of or participation in the activities and whether the activity was unethical. Program directors were surveyed about the use of ABSITE results for resident evaluation and promotion. RESULTS: Ten programs participated in the study. The resident response rate was 67% (186/277). Of the respondents, 43% felt that memorizing questions to study for future examinations was unethical and 50% felt that using questions another resident memorized was unethical. Most felt that buying (86%) or selling (79%) questions was unethical. Significantly more senior than junior residents have memorized (30% vs 16%; p = 0.04) or used questions others memorized (33% vs 12%; p = 0.002) to study for future ABSITE examinations and know of other residents who have done so (42% vs 20%; p = 0.004). Most programs used results of the ABSITE in promotion (80%) and set minimum score expectations and consequences (70%). CONCLUSION: Similar to our single-institution study, residents had not participated in activities they felt to be unethical; however the definition of what constitutes cheating remains unclear. Differences were identified between senior and junior residents with regard to memorizing questions for study. Cheating and unethical behavior is not always clear to the learner and represents an area for further education.

Surgical specialty procedures in rural surgery practices: implications for rural surgery training.

BACKGROUND: Specialty procedures constitute one eighth of rural surgery practice. Currently, general surgeons intending to practice in rural hospitals may not get adequate training for specialty procedures, which they will be expected to perform. Better definition of these procedures will help guide rural surgery training. METHODS: Current Procedural Terminology codes for all surgical procedures for 81% of North Dakota and South Dakota rural surgeons were entered into the Dakota Database for Rural Surgery. Specialty procedures were analyzed and compared with the Surgical Council on Resident Education curriculum to determine whether general surgery training is adequate preparation for rural surgery practice. RESULTS: The Dakota Database for Rural Surgery included 46,052 procedures, of which 5,666 (12.3%) were specialty procedures. Highest volume specialty categories included vascular, obstetrics and gynecology, orthopedics, cardiothoracic, urology, and otolaryngology. Common procedures in cardiothoracic and vascular surgery are taught in general surgical residency, while common procedures in obstetrics and gynecology, orthopedics, urology, and otolaryngology are usually not taught in general surgery training. CONCLUSIONS: Optimal training for rural surgery practice should include experience in specialty procedures in obstetrics and gynecology, orthopedics, urology, and otolaryngology.