Botulinum Toxin A Use in the Gastrointestinal Tract: A Reappraisal After Three Decades.

The discovery of botulinum toxin A (BTX)'s therapeutic properties has led to studies evaluating its usefulness in multiple medical disorders. Its use in the gastrointestinal (GI) tract has been studied for 30 years. Multiple databases, including PubMed, AccessMedicine, ClinicalKey, Cochrane Library, Embase, and Medline, were used to review research from case series to randomized controlled trials on BTX use in the GI tract. This article reviews the current literature on the efficacy of BTX and the strength of recommendations for or against its use in various disorders, including cricopharyngeal dysphagia, achalasia, nonachalasia motility disorders, gastroparesis, obesity, sphincter of Oddi disorders, chronic anal fissure, chronic idiopathic anal pain, and anismus. The appeal of BTX comes from its simplicity of administration, good safety profile, and reliability in decreasing muscular tone. However, there are several drawbacks that limit its use, including the lack of long-term efficacy and/or limited data in many GI disorders.

Characteristics and Outcomes of Cancer Patients With Venous Thromboembolic Events After Treatment With Immune Checkpoint Inhibitors.

OBJECTIVE: This study aimed to describe the clinical characteristics and outcomes of patients with venous thromboembolism (VTE) after Immune checkpoint inhibitors (ICI), focusing on patients with gastrointestinal (GI) immune-related adverse events (irAE). METHODS: In this retrospective, single-center study, we report the clinical outcomes of adult cancer patients who developed a VTE within 2 years of ICI initiation. Patients were excluded if alternate causes of VTE were present apart from malignancy and cancer therapy. The cohort was classified into those with GI-irAE, non-GI-irAE, and no irAE. A control group with ICI exposure without irAE and VTE was selected for comparative analysis. RESULTS: Of all ICI-treated patients, 1891 (17.2%) were diagnosed with VTE. In all, 501 (4.6%) had no etiology for VTE aside from malignancy and cancer therapy. Of these, 137 patients were included and classified as: 44 GI-irAE, 42 non-GI-irAE, and 51 no irAE. Chemotherapy within 6 months of ICI therapy was associated with increased VTE risk. There was no difference in the clinical course between those exposed to chemotherapy versus ICI therapy alone, time from ICI initiation to VTE, and VTE type, recurrence, or related hospitalization. While there was no difference in VTE-related mortality, the GI-irAE group was associated with lower all-cause mortality and superior overall survival. CONCLUSION: Combined ICI and chemotherapy use increased VTE risk. There is a similar disease course of VTE after ICI exposure, regardless of other irAEs. Co-existing GI-irAE with VTE is associated with superior overall survival. Prospective studies are needed to evaluate the relationship between ICI therapy and VTE and irAE impact on VTE outcomes.

Mesalamine and cholestyramine for immune checkpoint inhibitor-mediated diarrhea and colitis.

PURPOSE: Immune checkpoint inhibitors (ICI) are effective against various malignancies. However, adverse events including diarrhea and colitis can lead to significant morbidity and mortality. Recommendations for the management of ICI mediated diarrhea and colitis include steroids and biologics. Given their associated risks, this study evaluated the role of the non-immunosuppressive agents, mesalamine and or cholestyramine. METHODS: This is a retrospective, descriptive, single-center study of adults who developed ICI diarrhea and colitis between 2010 and 2020 at MD Anderson Cancer Center. Clinical data and outcomes were compared between those treated with the non-immunosuppressive therapies mesalamine and/or cholestyramine alone versus those who received additional immunosuppression with steroids and biologics. RESULTS: Our sample comprised 66 patients wherein, the mean age was 63 years, 71% were males, and 97% had stage III/IV cancers. Fourteen patients were treated successfully with non-immunosuppressive therapy. They had grade 1-3 diarrhea and 1-2 colitis with no difference in the rate of histologic colitis compared to those who received immunosuppressive therapy. They had less CTLA-4 inhibitor-based therapy (36% vs. 73%, p = 0.034), delayed onset of symptoms (159 vs. 64 days, p = 0.011), lower fecal calprotectin levels (56 vs. 234, p = 0.012) and were more likely to resume ICI therapy (64% vs. 25%, p = 0.006). CONCLUSION: Mesalamine and/or cholestyramine may be effective for mild ICI diarrhea and colitis among patients with delayed symptom onset with lower colonic inflammatory burden. Prospective studies randomizing patients with mild colitis between mesalamine/cholestyramine and immunosuppressive treatment are warranted to assess their efficacy and safety.

Endoscopy for the diagnosis and treatment of gastrointestinal bleeding caused by malignancy.

BACKGROUND AND AIM: The diagnosis and treatment of gastrointestinal (GI) bleeding secondary to malignancy can be challenging. Endoscopy is the gold standard to diagnose and treat gastrointestinal bleeding but clinical characteristics and outcomes of patients with malignancy-related bleeding are not well understood. This study aims to look at clinical characteristics, endoscopic findings, safety and clinical outcomes of endoscopic interventions for GI malignancy-related bleeding. METHODS: We retrospectively reviewed outcomes of patients with confirmed GI malignancies who underwent endoscopy for GI bleeding at MD Anderson Cancer Center between 2010 and 2019. Cox hazard analysis was conducted to identify factors associated with survival. RESULTS: A total of 313 patients were included, with median age of 59 years; 74.8% were male. The stomach (30.0%) was the most common tumor location. Active bleeding was evident endoscopically in 47.3% of patients. Most patients (77.3%) did not receive endoscopic treatment. Of the patients who received endoscopic treatment, 57.7% had hemostasis. No endoscopy-related adverse events were recorded. Endoscopic treatment was associated with hemostasis (P < 0.001), but not decreased recurrent bleeding or mortality. Absence of active bleeding on endoscopy, stable hemodynamic status at presentation, lower cancer stage, and surgical intervention were associated with improved survival. CONCLUSIONS: This study indicates that endoscopy is a safe diagnostic tool in this patient population; while endoscopic treatments may help achieve hemostasis, it may not decrease the risk of recurrent bleeding or improve survival.

Safety and efficacy of fecal microbiota transplantation to treat and prevent recurrent Clostridioides difficile in cancer patients.

Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline clinical data and risk factors related to rCDI and FMT were evaluated and compared between cancer types and between cases with remission and recurrence. Results: A total of 19 patients were studied: 12 with solid malignancies and 7 with hematologic malignancies. Most patients had stage IV cancer, and 21% of patients were in cancer remission. On average, patients had 2 episodes of CDI and received 3 courses of antibiotics within 1 year before FMT. 84% of patients with rCDI responded to FMT. Compared with patients who had CDI remission following FMT, non-remission cases were more likely to have received antibiotics following FMT. There were no serious adverse events or mortality within 30 days associated with FMT. Conclusions: FMT is safe, well-tolerated, and efficacious in treating rCDI in selected cancer patients. However, additional antibiotic use for complications from chemotherapy or immunosuppression negatively affected the efficacy of FMT in this population with advanced cancer.

Clinical Characteristics and Outcomes of Eosinophilic Colitis in Patients With Cancer.

BACKGROUND: Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria of colonic mucosa. The pathophysiology is unclear, but EoC has been associated with multiple known risk factors. AIM: The aim of this study was to characterize the clinical characteristics and disease course of patients with EoC at a major cancer center. MATERIAL AND METHODS: We retrospectively reviewed colonic samples obtained between January 2000 and December 2018 from our institutional database and included cases with significant colonic eosinophilia. Baseline clinical data and EoC-related clinical course and outcomes were documented. RESULTS: Forty-one patients were included. One fourth had coexisting autoimmune conditions. Seventy-eight percent had a cancer diagnosis. Half the patients received chemotherapy, with a median duration of 180 days between chemotherapy and EoC onset. Symptoms were present in 76% of patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs. 42%). Median duration of EoC symptoms was 30 days in patients with cancer and 240 days in those without cancer (P=0.03). Most patients (88%) had normal colonoscopy findings. Fifteen percent of patients required hospitalization. All-cause mortality was 37%, mostly related to underlying malignancy and organ failure. CONCLUSIONS: EoC in cancer patients appears to have more diarrhea-predominant symptoms, particularly in patients receiving chemotherapy, but a shorter disease duration compared with patients without cancer. Hospitalization can be required for serious cases. Treatment may be reserved for patients requiring symptom management, as most patients with EoC have good clinical outcomes regardless of treatment.

Lymphocytic Esophagitis Is Not Similar to Eosinophilic Esophagitis Except for Seasonal Variation.

OBJECTIVE: Unlike eosinophilic esophagitis (EoE), there is no consensus on the minimum number of intraepithelial lymphocytes (IEL) that is diagnostic of lymphocytic esophagitis (LyE). The aim of this study was to determine whether significant correlations exist between the numbers of intraepithelial lymphocytes (IEL) in esophageal biopsies and clinical and endoscopic manifestations usually associated with EoE. METHODS: H&E slides from esophageal biopsies from 330 patients were reviewed. The number of IEL and intraepithelial eosinophils (IEE) per mm2 was counted in the area with the highest concentration in each biopsy. The numbers were then correlated with clinical and endoscopic findings. RESULTS: As expected, a higher number of IEE was significantly associated with food impaction (p=0.001), dysphagia (p=0.021), esophageal stricture (p=0.017), rings (P<0.0001), and furrows (p<0.0001). By contrast, there was no significant association between increased IEL and any of the aforementioned clinical and endoscopic features in the original 330 patients or in a subset of 233 patients with no IEE. Interestingly, the number of both IEE and IEL varied significantly by the season when the biopsy was obtained, being lowest in the fall and highest in the spring (p=0002 for IEE and p<0.0001 for IEL). CONCLUSION: In esophageal biopsies, increased IEL has no significant correlation with food impaction or dysphagia or with esophageal stricture, rings, or furrows. There is significant variation in the number of IEL depending on the season when the biopsy is obtained, which has not been previously reported.

Oral Bile Reinfusion in Chronic Percutaneous Transhepatic Cholangiodrainage.

Percutaneous transhepatic cholangiodrainage is an intervention for obstructive jaundice that, although effective in decreasing bilirubin levels, often leads to depletion of regular bile acids that subsequently cause malabsorption, diarrhea, and acute kidney injury. Bile reinfusion (BR) is a method of enteral refeeding of biliary secretions to replenish innate bile acids to the patient. In addition, BR is a low-cost alternative to exogenous bile acid replacement and abates the need for inpatient fluid resuscitation. We report oral BR in a patient with percutaneous transhepatic cholangiodrainage due to choledocholithiasis and review the literature on BR.

Syphilis Causing Lichenoid Esophagitis.

We present a 50-year-old woman with human immunodeficiency virus admitted to the hospital for melenic stools and anemia who underwent esophagogastroduodenoscopy for evaluation of upper gastrointestinal bleed. She is found to have inflammation of the esophagus with ulcerations and crater formation. A biopsy reveals severe inflammation with lymphocytic infiltrates with civatte bodies suggestive of lichenoid esophagitis with the presence of spirochetes (Treponema pallidum). The presence of syphilis in the esophagus causing lichenoid esophagitis is an extremely rare presentation that has never been reported.

Clinical characteristics of colitis induced by taxane-based chemotherapy.

BACKGROUND: Limited data are available concerning the clinical features of toxic gastrointestinal (GI) effects of taxane-based therapy. We describe the clinical, endoscopic and histologic features of taxane-induced colitis. METHODS: This retrospective study included cancer patients who received taxane therapy and underwent colonoscopy for GI symptoms from 2000-2018. RESULTS: Of the 45,527 patients who received taxane therapy during the study period, 76 (0.2%) met the inclusion criteria. Most patients (54%) received paclitaxel, 37% docetaxel, and 9% nab-paclitaxel. The median time from taxane therapy initiation to colitis symptom onset was 31 days. The median duration of colitis symptoms was 30 days. Colitis treatment comprised immunosuppressive therapy in 8 patients (11%), antibiotics in 17 (22%), antimotility agents in 18 (24%), and octreotide or somatostatin in 2 (3%). Thirty-five patients (46%) required hospitalization and seven (9%) required admission to the intensive care unit (ICU). Endoscopy revealed mucosal ulceration in 19 patients (25%), nonulcerative inflammation in 32 (42%), and normal findings in 25 (33%). Seventeen patients (22%) had features of lymphocytic colitis. One patient had spontaneous colonic perforation that required surgical intervention. Colitis symptoms recurred in 7 patients (9%) after initial improvement. Patients who received nab-paclitaxel developed GI toxicity earlier (P=0.003), required colitis-related hospitalization more frequently (P=0.005), and received intravenous fluids more frequently (P=0.025), compared with patients who received other taxanes. CONCLUSIONS: Taxane-related colitis can present with significant inflammation on colonoscopy, and in a minority of patients as microscopic colitis. Taxane-induced colitis, although uncommon, can lead to ICU admission and colonic perforation.

Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines.

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

Pulmonary foreign body granulomatosis in a chronic user of powder cocaine.

We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

Pulmonary foreign body granulomatosis in a chronic user of powder cocaine / Granulomatose pulmonar de corpo estranho em um usuário crônico de cocaína em pó

ABSTRACT We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

RESUMO Descrevemos o caso de um homem de 33 anos de idade, usuário crônico de cocaína em pó, que apresentava dispneia, febre, sudorese noturna e perda de peso significativa. A TCAR de tórax revelou nódulos centrolobulares, dando uma impressão inicial de tuberculose miliar. Por isso, o paciente passou a receber tratamento empírico com quatro tuberculostáticos. Quatro semanas depois, apesar do tratamento antituberculose, o paciente continuou a apresentar os mesmos sintomas. Foi então realizada a biópsia pulmonar transbrônquica. A análise histopatológica da amostra obtida revelou granuloma de corpo estranho birrefringente. A história de uso de cocaína por inalação, a presença de nódulos centrolobulares e os achados histopatológicos de corpos estranhos confirmaram o diagnóstico de granulomatose pulmonar de corpo estranho. Este relato destaca o fato de que a granulomatose pulmonar de corpo estranho deve ser incluída no diagnóstico diferencial de perfis clínicos que se assemelham a tuberculose.

Meckel-Gruber syndrome: ultrasonographic and fetal autopsy correlation.

Meckel-Gruber syndrome (MGS) is a rare autosomal recessive disorder which is characterized by a classic triad of occipital encephalocele, polycystic kidneys and postaxial polydactyly. We describe a case of classic MGS, diagnosed on ultrasonography and genetic analysis, with subsequent confirmation and correlation by fetal autopsy.

MRI in flexor tendon rupture after collagenase injection.

Flexor tendon rupture is an unusual complication following collagenase injection to relieve contractures. These patients require a close follow-up and in the event of tendon rupture, a decision has to be made whether to repair the tendon or manage the complication conservatively. The authors report the utility of MRI in the prognostication and management of a patient with Dupuytren's contracture, who underwent collagenase injection and subsequently developed flexor digitorum profundus tendon rupture.

Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum.

BACKGROUND: COPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum. METHODS: 59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1. RESULTS: COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages. CONCLUSION: Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.