Number of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Treatments is Associated with Longer Survival: Analysis of a Large Prospective Cohort of Patients With Unresectable Peritoneal Surface Malignancies.

OBJECTIVE: To analyze the reasons for stopping pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivered for unresectable peritoneal surface malignancies (PSM) and to determine survival in a large patient cohort of an experienced PIPAC center. BACKGROUND: PIPAC alone or combined with systemic chemotherapy was developed to palliatively treat unresectable PSM. Safety, tolerance and promising survival results were already reported, but the reasons for stopping treatment remain unclear and the influence of the number of PIPAC procedures on prognosis has not been evaluated. METHODS: A retrospective analysis of PIPAC procedures from a prospectively maintained single institution PSM database was conducted from January 2016 to January 2023. RESULTS: A total of 346 patients underwent 1200 PIPAC treatments in the defined time period. Two-thirds of the patients completed 3 or more PIPAC procedures, and 2 patients had more than 15 treatment procedures. Reasons for PIPAC cessation were disease progression or complication (56%), reorientation to a potential curative procedure (19%), surgical complications of the procedure (13%), death between procedures (8%) and patient request (3%). PSM origin and receiving 3 or more PIPAC treatments were independently correlated with better survival in the overall population, in the group of ultimately unresectable PSM and after propensity score weighting. CONCLUSION: The main reason for stopping PIPAC treatment in palliative management of PSM is disease progression. When 3 or more PIPAC procedures can be delivered in combination to systemic chemotherapy, survival is significantly improved. Its use should be validated by prospective studies.

Esophagectomy in the Older Adult: A Systematic Review.

Current management of esophageal carcinoma (EC) involves combining different modalities, offering the opportunity of personalized strategies. This is particularly enticing in the geriatric population, where tailoring treatment modalities remains key to achieve good outcomes in terms of both quality of life and survival. Primary outcomes of our review included (1) evidence on short-term outcomes following esophagectomy, and (2) evidence on long-term outcomes following esophagectomy. Secondary review questions compared outcomes of (1) neoadjuvant treatment versus upfront surgery for locally advanced esophageal carcinoma, (2) endoscopic submucosal dissection versus esophagectomy for early esophageal carcinoma, and (3) definitive radiation with or without chemotherapy versus surgery. Twenty-six articles were included in the review for the main review questions. Our systematic review underscores the need for comprehensive geriatric evaluations to guide decision-making. Despite concerns about perioperative risks, well-selected older patients can derive survival benefits from surgical intervention.

Esophageal cancer in octogenarians: Should esophagectomy be done?

INTRODUCTION: Esophagectomy is the treatment of choice for esophageal cancer. In octogenarians data is conflicting. We evaluated postoperative outcomes and long-term survival of octogenarians and their younger counterparts. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database including consecutive patients with esophageal cancer who underwent esophagectomy at a large referral, academic center between 2012 and 2021. Subgroups were designed according to age (<70, 70-79, and ≥ 80). RESULTS: A total of 359 patients underwent esophagectomy for esophageal cancer, 223 (62%) aged <70, 107 (30%) aged 70-79 and 29 (8%) aged ≥80. Octogenarians had higher American Society of Anesthesiologists [ASA] scores (p = 0.001), and fewer received neoadjuvant therapy (p = 0.04). Octogenarians experienced more major complications (P < 0.001) with significantly higher 30-day mortality rate (P = 0.001). In a multivariable analysis, major complications were associated with higher risk of being discharged to a rehabilitation center (odds ratio [OR] 14.839, 95% confidence interval [CI] 4.921-44.747, p < 0.001) while age was not. Overall survival was reduced in octogenarians, with a 50th percentile survival of 10 months compared to 32 and 26 months in patients age < 70 and 70-79, respectively (p = 0.014). In a multivariable analysis, age ≥ 80 (hazard ratio [HR] 4.478 95% CI 2.151-9.322, p < 0.001), cancer stage (HR 1.545, 95% CI 1.095-2.179, p = 0.013), and postoperative major complications (HR 2.705 95% CI 1.913-3.823, p < 0.001) were independently associated with reduced survival. DISCUSSION: Our study showed that octogenarians had significantly higher postoperative major complications compared to younger age groups. Overall survival was significantly reduced in these patients, probably due to an increased rate of perioperative mortality. Better patient selection and preparation may improve postoperative outcomes and increase long-term survival.

Giant colonic diverticulitis, an extremely rare presentation of a rare disease: clinical presentation and literature review

Introduction: Giant colonic diverticulum (GCD) is rare phenomenon, with less than 200 cases described in the literature. One of the complications of GCD is diverticulitis. To date, there is paucity of data addressing the diagnosis and management of GCD complicated by acute diverticulitis. Objective: To better understand the diagnostic tools, the initial management, and the long-term follow-up for this group of patients as well as to recommend a proper multidisciplinary approach to this infrequent disease. Method A systematic literature search was performed using the PubMed, Embase, and Cochrane databases to identify all the published studies on GCD complicated by diverticulitis. Two of the authors assessed the relevance of the included full-text papers. The articles were assessed independently. Results: In total, 12 cases were identified. Our results show that 10/11 (91%) of the patients who had computed tomography (CT) scans during the initial evaluation had a correct diagnosis. There was no case of failure to non-operative approach (7/7). The patients who had an emergency operation were treated so due to diffuse peritonitis (two patients), acute hemorrhage arising from ulcers within the diverticula (one patient), and misdiagnosis (one patient). Conclusion: Giant colonic diverticulitis is a very rare disease. Computed tomography scan is a valuable tool for the initial diagnosis as well as for treatment strategy planning. Non-operative management is a viable option for patients without diffuse peritonitis. Interval endoscopy is recommended if no contraindication exists. (AU)

Implantation of an Impedance Sensor for Early Detection of Gastrointestinal Anastomotic Leaks.

INTRODUCTION: Accurate early diagnosis of a gastrointestinal anastomotic leak remains a challenge. When an anastomotic leak develops, the electrical properties of the tissue undergoing inflammatory processes change, resulting from the extravasation of inflammatory fluid and cellular infiltration. The method described here intends to provide a novel early anastomotic leak warning system based upon measurable changes in tissue impedance nearby an acute inflammatory process. METHODS: A biodegradable Mg-alloy was compared with a nonabsorbable stainless steel (STS) electrode connected to a wireless recording system for impedance measurement. In vitro measurements were made in physiological solutions and small animal (eight mice) and large animal (eight pigs) models with an anastomotic leak simulated by an open colotomy. Measurements were made at 10 mm intervals from the open colon at baseline and up to 120 min comparing these with a sutured colonic wound and normal tissue. RESULTS: In-vitro biodegradable magnesium electrode impedance evaluation showed good sensitivity to different media due to its environmental corrosion properties. The impedance of an acidic environment (1.06 ± 0.02 kΩ for citric acid) was twice that of phosphate-buffered saline (PBS) (0.64 ± 0.008 kΩ) with a distinction between Normal Saline (0.42 ± 0.013 kΩ) and PBS (0.64 ± 0.008 kΩ). This was in contrast to the performance characteristics of the control STS electrodes, where impedance in an acidic environment was lower than saline or PBS (citric acid:0.76 ± 0.01 kΩ versus PBS: 1.32 ± 0.014 kΩ). In a mouse model simulating an anastomotic leak, there was a significant increase in impedance after 120 min when compared with controls (99.7% increase versus 9.6% increase, respectively; P < 0.02). This effect was confirmed in a pig model when relative impedance measurements of the leak and control groups were compared (1.86 ± 0.46 versus 1.07 ± 0.02, respectively; P < 0.027). CONCLUSIONS: Electrophysiological measurement shows diagnostic sensitivity for a gastrointestinal leak with potential clinical utility in the postoperative detection of early intra-abdominal sepsis. Further investigation of biodegradable tissue sensors capable of monitoring an early anastomotic leak is required.

Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents.

Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we showed in mice that fetal or adult lung progenitors could potentially provide donor cells for transplantation, provided that the lung stem cell niche in the recipient is vacated of endogenous lung progenitors by adequate conditioning. Accordingly, marked lung regeneration could be attained following i.v. infusion of a single cell suspension of lung cells into recipient mice conditioned with naphthalene (NA) and 6Gy total body irradiation (TBI). As clinical translation of this approach requires the use of allogenic donors, we more recently developed a novel transplantation modality based on co-infusion of hematopoietic and lung progenitors from the same donor. Thus, by virtue of hematopoietic chimerism, which leads to immune tolerance toward donor antigens, the lung progenitors can be successfully engrafted without any need for post-transplant immune suppression. In the present study, we demonstrate that it is possible to replace NA in the conditioning regimen with Cyclophosphamide (CY), approved for the treatment of many diseases and that a lower dose of 2 GY TBI can successfully enable engraftment of donor-derived hematopoietic and lung progenitors when CY is administered in 2 doses after the stem cell infusion. Taken together, our results suggest a feasible and relatively safe protocol that could potentially be translated to clinical transplantation of lung progenitors across major MHC barriers in patients with terminal lung diseases.

Outcomes of surgery in patients 90 years of age and older: A retrospective cohort study.

BACKGROUND: Important trade-offs of risks versus benefits of surgery need to be discussed with older adults, in particular nonagenarians who are candidates for surgery. Data that examine specific outcomes of surgical interventions in this age group are sparse. We aimed to evaluate the clinical presentation and postoperative outcomes of nonagenarians undergoing surgery. METHODS: A retrospective cohort study of consecutive patients 90 years of age and older who underwent surgery between 2014 and 2018 in general surgical ward of a large-volume academic center. Subgroups were designed according to type of surgery (elective versus emergency surgery) and diagnosis (oncology versus non-oncology). Preoperative assessments included Malnutrition Universal Screening Tool, Norton Scale, Morse Scale, Katz, and Lawton-Brody indices. RESULTS: A total of 198 nonagenarians underwent surgery, of which 38% were elective and 62% were emergency surgery. Median follow-up was 26 months. More patients in the elective group compared with the emergency group had oncology diagnoses (42.1% and 14.7%, respectively, P < .001), resided preoperatively at home (93.4% and 77.9%, respectively, P = .003), and were functionally independent (71.1% and 41.8%, respectively, P = .0005). Postoperative 30-day mortality frequency was 6.6% in the elective group and 39.3% in the emergency group (P < .001). Two-year survival frequency of non-oncology group was 72.7% in elective surgeries and 40.6% in emergency surgeries (P < .001). Two-year survival frequency of oncology group was 37% in elective surgeries and 27.8% in emergency surgeries (P = .12). CONCLUSION: Elective surgery in adults aged 90 and above can be safely performed with acceptable 2-year outcomes. Emergency surgery for oncology diagnoses carries dismal outcomes, so palliative approaches should be considered.

The impact of cervical anastomotic leak after esophagectomy on long-term survival of patients with esophageal cancer.

BACKGROUND: Anastomotic leak is a major complication after esophagectomy. There is a paucity of data on long-term oncological outcomes of cervical anastomotic leak after esophagectomy for cancer. We evaluated the impact of such a leak on postoperative outcomes as well as on long-term oncological outcomes. METHODS: A retrospective analysis of a prospectively maintained database of patients with esophageal cancer who underwent esophagectomy with a cervical esophagogastric anastomosis between 2010 and 2017. Patients were divided into 3 groups: patients with no anastomotic leak; patients with nonsevere (type 1 & 2) leak, and patients with severe (type 3) leak. A comparison of postoperative and long-term oncological outcomes was made between the groups. RESULTS: Two hundred and eight patients were included in this study. Thirty-two (15%) patients had cervical anastomotic leak, of which 20 (63%) had type 1 and 2 (nonsevere) leak, and 12 (37%) had type 3 (severe) leak. Overall, 30-day mortality rate was 7%. Mortality rate was 4% in patients without leak, 15% in patients with nonsevere leak, and 25% in patients with severe anastomotic leak (P = .007). Overall median survival was 42 months. Patients with severe leak had poorer overall survival compared to patients with nonsevere and no anastomotic leak (6, 38, and 39 months, respectively, P = .011). There was no difference in disease-free survival of patients with or without anastomotic leak. CONCLUSION: Leakage from cervical anastomosis after esophagectomy had no impact on disease-free survival of patients with esophageal cancer. Severe anastomotic leak was associated with lower overall survival, probably due to a high rate of postoperative mortality.

Some Nursing Screening Tools Can Be Used to Assess High-Risk Older Adults Who Undergo Colorectal Surgery for Cancer.

AIM: Life expectancy and incidence of cancer among older adults are increasing. The aim of this study was to assess whether routinely used nursing screening tools can predict surgical outcomes in older adults with colorectal cancer. METHODS: Data of patients who underwent elective colorectal cancer surgery at Rabin Medical Center during the years 2014-2016 were collected retrospectively. Patients were divided into study group (age 80-89 y), and control group (age 60-69 y) for comparing surgical outcomes and six-month mortality. In the study group, screening tool scores were evaluated as potential predictors of surgical outcomes. These included Malnutrition Universal Screening Tool (MUST), Admission Norton Scale Scores (ANSS), Morse Fall Scale (MFS), and Charlson Co-morbidity Index (CCI). RESULTS: The study group consisted of 77 patients, and the control group consisted of 129 patients. Postoperative mortality and morbidity were similar in both groups. Nursing screening tools did not predict immediate postoperative outcomes in the study group. MUST and CCI were predictors for six-month mortality. CCI score was 9.43±2.44 in those who died within six months from surgery compared to 7.07 ±1.61 in those who were alive after six months (p<0.05). Post-operative complications were not associated with increased 30-day mortality. Advanced grade complications were associated with an increased six-month mortality (RR=1.37, 95% CI 0.95-1.98, p=0.013). CONCLUSION: Different screening tools for high-risk older adults who are candidates for surgery have been developed, with the caveat of necessitating skilled physicians and resources such as time. Routinely used nursing screening tools may be helpful in better patient selection and informed decision making. These tools, specifically MUST and CCI who were found to predict six-month survival, can be used to additionally identify high-risk patients by the nursing staff and promote further evaluation. This can be a valuable tool in multidisciplinary and patient-centered care.

Multi-lineage Lung Regeneration by Stem Cell Transplantation across Major Genetic Barriers.

Induction of lung regeneration by transplantation of lung progenitor cells is a critical preclinical challenge. Recently, we demonstrated that robust lung regeneration can be achieved if the endogenous stem cell niches in the recipient's lung are vacated by sub-lethal pre-conditioning. However, overcoming MHC barriers is an additional requirement for clinical application of this attractive approach. We demonstrate here that durable tolerance toward mis-matched lung progenitors and their derivatives can be achieved without any chronic immune suppression, by virtue of co-transplantation with hematopoietic progenitors from the same donor. Initial proof of concept of this approach was attained by transplantation of fetal lung cells comprising both hematopoietic and non-hematopoietic progenitors. Furthermore, an even higher rate of blood and epithelial lung chimerism was attained by using adult lung cells supplemented with bone marrow hematopoietic progenitors. These results lay the foundation for repair of lung injury through a procedure akin to bone marrow transplantation.

Long-Term Effectiveness of Laparoscopic Conversion of Sleeve Gastrectomy to a Biliopancreatic Diversion with a Duodenal Switch or a Roux-en-Y Gastric Bypass due to Weight Loss Failure.

BACKGROUND: Gastroesophageal reflux disease and inadequate weight loss (IWL) are long-term complications of laparoscopic sleeve gastrectomy (LSG) and indications for a laparoscopic conversion to an alternative bariatric procedure. The aim of this study is to report the long-term outcomes of biliopancreatic diversion with a duodenal switch (DS) or a Roux-en-Y gastric bypass (RYGB) as conversion procedures for weight loss failure after LSG. METHODS: The data of all patients who underwent post-LSG conversion to either a RYGB or a DS at our institution between November 2006 and May 2016 was retrospectively analyzed. Included were all patients with > 1-year follow-up who were operated due to IWL or weight regain. Patients with the indication of reflux were excluded. RESULTS: Sixty-six patients underwent conversion from LSG to RYGB, DS, or one-anastomosis gastric bypass during the study period. There were 21 revisions to DS and 18 to RYGB that met the inclusion criteria. The respective weight and body mass index (BMI) before and after LSG were 125 and 110 kg and 46 and 40.5 kg/m2 in the RYGB group and 148 and 126 kg and 53.7 and 46 kg/m2 in the DS group. At the last follow-up (> 2 years), 15 RYGB patients had a reduction in BMI of 8.5-31.9 kg/m2 and 18 DS patients had a reduction in BMI of 12.8-31.9 kg/m2. The mean follow-up was 48.5 months (range 24-76). All comorbidities improved or underwent complete remission. CONCLUSION: Conversion from SG to RYGB or DS is an efficient and effective treatment for IWL and improvement of comorbidities. Further studies are warranted to evaluate long-term weight regain.

Lung Injury Repair by Transplantation of Adult Lung Cells Following Preconditioning of Recipient Mice.

Repair of injured lungs represents a longstanding therapeutic challenge. We recently demonstrated that human and mouse embryonic lung tissue from the canalicular stage of development are enriched with lung progenitors, and that a single cell suspension of canalicular lungs can be used for transplantation, provided that lung progenitor niches in the recipient mice are vacated by strategies similar to those used in bone marrow transplantation. Considering the ethical limitations associated with the use of fetal cells, we investigated here whether adult lungs could offer an alternative source of lung progenitors for transplantation. We show that intravenous infusion of a single cell suspension of adult mouse lungs from GFP+ donors, following conditioning of recipient mice with naphthalene and subsequent sublethal irradiation, led to marked colonization of the recipient lungs, at 6-8 weeks post-transplant, with donor derived structures including epithelial, endothelial, and mesenchymal cells. Epithelial cells within these donor-derived colonies expressed markers of functionally distinct lung cell types, and lung function, which is significantly compromised in mice treated with naphthalene and radiation, was found to be corrected following transplantation. Dose response analysis suggests that the frequency of patch forming cells in adult lungs was about threefold lower compared to that found in E16 fetal lungs. However, as adult lungs are much larger, the total number of patch forming cells that can be collected from this source is significantly greater. Our study provides proof of concept for lung regeneration by adult lung cells after preconditioning to vacate the pulmonary niche. Stem Cells Translational Medicine 2018;7:68-77.

Novel immunoregulatory role of perforin-positive dendritic cells.

The recently described generation of a highly defined population of dendritic cells which express perforin and granzyme A (termed "perf-DCs") and their ability to selectively delete cognate CD8+ T cell has raised the possibility that these cells play a role in the maintenance of peripheral tolerance. Using bone marrow transplantation, we generated mice selectively lacking perforin expressing dendritic cells. These mice progressively gain weight and exhibit features resembling metabolic syndrome as well as an enhanced susceptibility to autoimmunity induction. Interestingly, these pathological phenotypes were reversed upon treatment with CD4/CD8 neutralizing antibodies. Thus, it appears that this rare subpopulation of dendritic cells (perf-DCs) displays a major regulatory role in adipose tissue inflammatory processes and in autoimmunity.

Acute mastoiditis in children under 15 years of age in Southern Israel following the introduction of pneumococcal conjugate vaccines: a 4-year retrospective study (2009-2012).

OBJECTIVES: To describe the epidemiologic, microbiologic, clinical and therapeutic aspects of acute mastoiditis (AM) in children <15 years of age during the 4-year period (2009-2012) following the introduction of pneumococcal conjugate vaccines in Israel. PATIENTS AND METHODS: The medical records of all children with a discharge diagnosis of AM were reviewed. RESULTS: A total of 66 AM episodes occurred in 61 patients. Forty-four (66.6%) cases occurred among patients <4 years, recent acute otitis media (AOM) history was reported in 27.1% and 28.8% patients received previous antibiotics for AOM. Postauricular swelling, postauricular sensitivity, protrusion of auricle and postauricular edema (93.8%, 90.6%, 85.9% and 95.7%, respectively) were the most common signs of AM. Leukocytosis >15,000 WBC/mm(3) was found in 39 (59.1%) cases. Cultures were performed in 52/66 episodes (positive in 27, 51.92% episodes), with recovery of 32 pathogens. The most frequently isolated pathogens were Streptococcus pneumoniae (15/52, 28.85%), Streptococcus pyogenes (9, 17.3%) and nontypeable Haemophilus influenzae (5, 9.62%). Eight (53.3%) S. pneumoniae isolates were susceptible to penicillin. Mean incidence of overall and pneumococcal AM were 11.1 and 2.58 cases/100000, with no significant changes during the study years. Surgical intervention was required in 19 (28.8%) patients. CONCLUSIONS: (1) AM occurs frequently in patients without previous AOM history and with no previous antibiotic treatment; (2) S. pneumoniae and S. pyogenes continued to be the main etiologic agents of AM during the postvaccination period; (3) No changes were recorded in overall AM incidence and in pneumococcal AM incidence during the postvaccination period.