New and emerging therapies for the treatment of relapsed/refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first line chemoimmunotherapy, necessitating second-line salvage therapy. This has historically consisted of platinum-based chemotherapy regimens followed by autologous hematopoietic stem cell transplantation with curative intent for transplant-eligible patients or palliative chemotherapy for transplant-ineligible patients. In recent years there have been several new therapeutic agents approved for the treatment of relapsed/refractory DLBCL, thereby expanding the therapeutic landscape. These agents include polatuzumab vedotin, tafasitamab, loncastuximab tesirine, selinexor, and anti-CD19 chimeric antigen receptor T-cell therapies such as axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. This review summarizes the pharmacology, efficacy, safety, dosing, and administration of new agents recently approved for the treatment of relapsed/refractory DLBCL.

Outcomes of colostomy takedown following Hartmann's procedure: successful restoration of continuity comes with a high risk of morbidity.

AIM: Restoration of bowel continuity following a Hartmann's procedure is a major surgical undertaking associated with significant morbidity. The aim of this study was to review the authors' experience with Hartmann's reversal. METHOD: This was a retrospective review of consecutive patients from institutional databases who were selected to undergo open or laparoscopic Hartmann's reversal at two tertiary academic referral centres and a public safety net hospital (2010-2019). The main outcome measure was the rate of successful stoma reversal. Secondary outcomes included 30-day postoperative outcomes and procedural details. RESULTS: One hundred and fifty patients underwent attempted reversal during the study period, which was successful in all but three patients (98%). Patients were 59% Hispanic and 73% male, with a mean age of 48.7 ± 14.1 years, mean American Society of Anesthesiologists classification of 2.2 ± 0.6 and mean body mass index (BMI) of 28.6 ± 5.3 kg/m2 , with 39% of patients having a BMI > 30 kg/m2 . The mean time interval between the index procedure and reversal was 14.4 months, 53% of the index cases were performed at outside institutions and the most common index diagnoses were diverticulitis (54%), abdominal trauma (16%) and colorectal malignancy (15%). In 22% of cases a laparoscopic approach was used, with 42% of these requiring conversion to open. Proximal diverting stomas were created in 32 patients (21%), of which 94% were reversed. The overall morbidity rate was 54%, comprising ileus (32%), wound infection (15%) and anastomotic leak (6%), with a major morbidity rate (Clavien-Dindo ≥ 3) of 23%. CONCLUSION: Hartmann's reversal remains a highly morbid procedure. Our results suggest that operative candidates can be successfully reversed, but there is significant morbidity associated with restoration of intestinal continuity, particularly in obese patients. A laparoscopic approach may decrease morbidity in selected patients but such cases have a high conversion rate.

Oral Endocrine Therapy Agent, Race/Ethnicity, and Time on Therapy Predict Adherence in Breast Cancer Patients in a Large Academic Institution.

INTRODUCTION: Adherence to oral endocrine therapy (OET) reduces recurrence risk for hormone receptor (HR)-positive breast cancer (BC). Refill data accessed through electronic health records may provide objective assessment of OET adherence. Our goal was to (1) determine the feasibility of reviewing electronic health records for assessing OET adherence, (2) evaluate 6 months' OET adherence in HR-positive BC patients, and (3) identify predictors of low adherence. PATIENTS AND METHODS: A single-center, retrospective study from May through December 2018 was conducted. Primary end point was adherance rate at 6 months. Chi-square and Student t tests were used to compare adherent and nonadherent groups. Multivariable logistic regression models were used to assess predictors of adherence. RESULTS: Of 492 patients, 338 patients were included in adherence analysis. Of 338 patients identified, 82% (n = 277) were adherent at 6 months. In the multivariable logistic model, race/ethnicity, type of endocrine therapy, and time on therapy were found to be significantly associated with adherence. Asian/non-Hispanic and white/Hispanic patients were less likely to be adherent compared to white/non-Hispanics (Asian/non-Hispanic: odds ratio [OR], 0.3; 95% confidence interval [CI], 0.11-0.82; white/Hispanic: OR, 0.27; 95% CI, 0.11-0.64). Patients prescribed aromatase inhibitors were more likely to be adherent compared to patients prescribed tamoxifen (OR, 2.06; 95% CI, 1.02-4.14). Last, patients prescribed OET for 3 to 5 years had lower adherence compared to patients given OET for 2 years or less (OR, 0.29; 95% CI, 0.09-0.91). CONCLUSION: Accessing refill data through electronic health records was found to be feasible. Tamoxifen therapy, Asian/non-Hispanic and white/Hispanic origin, and longer time on therapy predicted nonadherence in our patients.

Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis.

Rabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

Operative management of diverticulitis in a tertiary care center.

BACKGROUND: Diverticulitis has become a medically managed disease process; the indications and timing of surgical intervention have evolved. METHODS: We retrospectively reviewed all patients who underwent surgical intervention due to diverticular disease by the Division of Colon and Rectal Surgery from 2012 to 2014. RESULTS: Ninety-eight surgeries were performed. Indications included colovesicular fistula, multiple recurrences of diverticulitis, medically refractory diverticulitis, stricture, abscess, colocutaneous fistula, and colovaginal fistula. Average length of stay was 5.7 ± 5.9 days (range, 1 to 51). Eighteen patients (18%) required an ostomy. Postoperative complications occurred in 18% of patients, including anastomotic leak (3.3%), wound infection (7.1%), acute kidney injury (5.1%), and urinary tract infection (2.0%). Thirty-day readmission rate was 7.2%; unplanned 30-day reoperation rate was 3.1%. There were no deaths. CONCLUSIONS: The type of patient undergoing surgery for diverticulitis has changed, with selection bias toward chronic, advanced disease due to the proliferation of medical management strategies.

Factors Associated with a Short (<2 Days) or Long (>10 Days) Length of Stay after Colectomy: A Multivariate Analysis of over 400 Patients.

A prospectively maintained database of 415 patients undergoing colectomy was evaluated. We performed a logistic regression analysis to identify factors associated with 1) length of stay (LOS) of 2 days or less and 2) LOS of 10 days or more. Investigated variables included demographics, American Society of Anesthesiology (ASA) score, diagnosis, operative procedure, approach and time, transfusion requirements, and occurrence of any complications. Factors associated with a LOS of two days or less included ASA [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.208-0.576], use of transversus abdominis plane block (OR: 5.259, 95% CI: 2.825-9.791), and operative time (OR: 0.98, 95% CI: 0.974-0.986). Age >65 had an OR of 1.73, though this did not reach statistical significance. Factors associated with LOS >10 days included ASA (OR: 2.152, 95% CI: 1.245-3.721), anastomotic leak (OR: 2.163, 95% CI: 1.486-3.148), ileus (OR: 8.790, 95% CI: 4.501-17.165), and surgical site infection (OR: 5.846, 95% CI: 2.764-12.362). Cancer and transfusion status were associated but did not reach statistical significance. Although operative time was longer in left-sided resections, no differences in LOS were observed. In conclusion, numerous factors are associated with short or long LOS and may help stratify resource utilization after colectomy. Further study is needed to confirm our findings.

Laparoscopic right hemicolectomy: short- and long-term outcomes of intracorporeal versus extracorporeal anastomosis.

BACKGROUND: The use of laparoscopy for right hemicolectomy has gained popularity allowing the option of a totally laparoscopic intracorporeal anastomosis (IA) for intestinal reconstruction. This technique may alleviate some of the technical limitations that a surgeon faces with a laparoscopic-assisted extracorporeal anastomosis (EA). METHODS: A retrospective chart review of 195 consecutive patients who underwent laparoscopic right hemicolectomy by four colorectal surgeons at three institutions from March 2005 to June 2014 was performed. Multivariate regression analysis was used to compare postoperative and oncologic outcomes. RESULTS: A total of 195 patients underwent laparoscopic right hemicolectomy over the study period, with 86 (44 %) patients receiving IA and 109 (56 %) patients receiving an EA. The most common indication for surgery in both groups was cancer: 56 (65 %) of IA cases and 57 (52 %) of EA cases. IA had a significantly higher rate of minor complications but no difference in serious complications compared to EA. Conversion to open resection was higher in EA. Using multivariate analysis to compare IA versus EA, there was no significant difference in length of stay, return of bowel function, risk of anastomotic leak, risk of intraabdominal abscess or risk of wound complications. Amongst cancer resections, there was no significant difference in the median number of lymph nodes harvested (18 LNs in IA group vs. 19 LNs in EA group, P > 0.05). There was also no significant difference in overall survival and disease-free survival at 5.7 years between the two groups. CONCLUSIONS: IA in laparoscopic right hemicolectomy is associated with similar postoperative and oncologic outcomes compared to EA. IA may possess advantages in terms of conversion and flexibility of specimen extraction, but this is counterbalanced by a higher incidence of minor complications. These findings suggest that IA represents a valid technique in the arsenal of the experienced colorectal surgeon without compromising outcomes.

Risk factors for prolonged ileus following colon surgery.

BACKGROUND: Prolonged ileus is one of the most common postoperative complications after colorectal surgery. We sought to investigate the predictors of prolonged ileus following elective colon resections procedures. METHODS: The national participant user files of NSQIP databases were utilized to examine the clinical outcomes of patients undergoing elective colon resection during 2012-2013. Multivariate regression analysis was performed to investigate predictors of prolonged ileus. Prolonged ileus was defined as no return of bowel function in 7 days. RESULTS: We sampled a total of 27,560 patients who underwent colon resections; of these, 3497 (12.7%) patients had prolonged ileus. Patients with ileocolonic anastomosis (ICA) had a significantly higher rate of prolonged ileus compared to patients with colorectal anastomosis (CRA) (15 vs. 11.5%, AOR 1.25, P < 0.01). Prolonged ileus was significantly associated with intra-abdominal infections (13 vs. 2.8%, AOR 2.56, P < 0.01) and anastomotic leakage (12 vs. 2.4%, AOR 2.50, P < 0.01). Factors such as preoperative sepsis (AOR 1.63, P < 0.01), disseminated cancer (AOR 1.24, P = 0.01), and chronic obstructive pulmonary disease (AOR 1.27, P = 0.02) were associated with an increased risk of prolonged ileus, whereas oral antibiotic bowel preparation (AOR 0.77, P < 0.01) and laparoscopic surgery (AOR 0.51, P < 0.01) are associated with decreased prolonged ileus risk. CONCLUSIONS: Prolonged ileus is a common condition following colon resection, with an incidence of 12.7%. Among colon surgeries, colectomy with ICA resulted in the highest rate of postoperative prolonged ileus. Prolonged ileus is positively associated with anastomotic leak and intra-abdominal infections; thus, a high index of suspicion must be had in all patients with prolonged postoperative ileus.

Laparoscopic Versus Open Loop Ileostomy Reversal: Is there an Advantage to a Minimally Invasive Approach?

BACKGROUND: Ileostomy reversals are commonly performed procedures after colon and rectal operations. Laparoscopic ileostomy reversal (LIR) with lysis of adhesions has potential benefits over conventional open surgery. The aim of this study was to compare outcomes of laparoscopic and open ileostomy reversal. METHODS: 133 consecutive patients undergoing ileostomy reversal at our institution between June 2009 and August 2013 were analyzed using a retrospective database. The group comprised 53 laparoscopic cases and 80 open cases, performed by four surgeons at a single center. The data were analyzed for patient demographics, operative characteristics, postoperative outcomes, and 30-day morbidity and mortality. RESULTS: The two groups had comparable mean age, gender distribution, ASA scores, and BMI. The laparoscopic group had a significantly longer duration of surgery compared to the open reversal group (109 versus 93 min, p < 0.05). However, this group underwent more lysis of adhesions (60.4 % versus 26.3 %, p < 0.01) as well as concurrent stoma site mesh reinforcement (32.1 % versus 6.3 %, p < 0.01). In the laparoscopy group, 20.7 % of patients underwent intra-corporeal ileo-ileal anastomosis. There were no significant differences between the laparoscopic and open groups with regard to estimated blood loss (31 versus 40 ml, respectively) or mean length of stay (5.3 vs. 5.7 days, respectively). The rates of overall 30-day morbidity (16.9 % for laparoscopic vs. 21.3 % for open) as well as rates of specific complications were equivalent between groups. 30-day mortalities were not noted in either group. CONCLUSION: LIR is safe and effective with low perioperative morbidity and mortality. The use of laparoscopy as an option in terms of concomitant hernia repair and lysis of adhesions may be considered in selected patients.

Surgical site infection impact of pelvic exenteration procedure.

BACKGROUND: We sought to investigate morbidity and infectious complications following pelvic exenteration (PEx) and compare infectious complications of patients undergoing PEx and conventional rectal resections. METHODS: The NSQIP database was utilized to examine the clinical data of patients undergoing elective rectal resections during 2005-2013. Multivariate regression analysis was used to compare postoperative complications of patients who underwent PEx and proctectomy procedure. RESULTS: We sampled a total of 7,950 patients who underwent rectal resection. Of these, 303 (3.8%) patients underwent pelvic exenteration. Mortality, morbidity, and infectious complications of patients who underwent pelvic exenteration were 1.7%, 65.7%, and 42.6%, respectively. Patients who underwent PEx had a significantly higher rate of morbidity (AOR: 2.01, P < 0.01), overall infectious complications (AOR: 1.49, P < 0.01), hemorrhagic complications (AOR: 3.36, P < 0.01), and surgical site infections (SSI) (AOR: 1.23, P = 0.04) compared to patients who underwent proctectomy. Return to operation room (AOR: 4.99, P < 0.01), obesity (AOR: 1.43, P < 0.01), disseminated cancer (AOR: 1.30, P = 0.01) were significantly associated with SSI complications. CONCLUSION: Postoperative morbidity and infectious complication are significantly higher after PEx procedure. Return to operation room, obesity, and disseminated cancer are strongly associated with surgical site infections complications in rectal surgery. Specific consideration to infectious complications is recommended for these patients.

Colorectal surgery in Parkinson's disease--outcomes and predictors of mortality.

PURPOSE: Although diseases of the lower gastrointestinal tract are common in patients with Parkinson's disease, there is a paucity of data regarding postoperative outcomes after colorectal surgery. METHODS: The Nationwide Inpatient Sample database (2007-2011) was utilized to analyze outcomes in patients with Parkinson's disease (PD) undergoing colorectal surgery. Main outcomes were risk-adjusted inpatient morbidity, mortality, hospital charge, and length of hospital stay. RESULTS: A total of 6490 patients were identified. Utilization of laparoscopic surgery in Parkinson's patients has progressively increased in frequency over the latest 5 years analyzed. The most common diagnoses were colorectal malignancy (39 %) and intestinal obstruction (20 %). Right hemicolectomy (37 %) and sigmoidectomy (30 %) were the most common operations. Laparoscopy was used in 18 % of Parkinson's patients and most commonly in the elective setting. 54.3 % of Parkinson's patients had emergency surgery compared to 38.6 % in non-Parkinson's. Overall morbidity and mortality were significantly lower after laparoscopic surgery compared to open (20 vs. 25 % and 2.1 vs. 6.6 %, respectively). Length of stay was significantly shorter (OR -1.86; p < 0.01) for laparoscopic operations, but there were no significant differences in risk-adjusted outcomes between laparoscopic and open groups. CONCLUSION: PD patients have high rates of morbidity and mortality after colorectal surgery; this may be because more than half of all patients in this population undergo emergent surgery. The laparoscopic approach appears to have short-term benefits in this patient population.