Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers.

INTRODUCTION: Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds-urging the quest for predictive biomarkers. We hypothesize that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response. PATIENTS AND METHODS: In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients. RESULTS: The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P < 0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P = 0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P < 0.001), resulting in a 1-year survival difference of 24% (P = 0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy. CONCLUSIONS: These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.

A systematic review on laparoscopic subtotal cholecystectomy for difficult gallbladders: a lifesaving bailout or an incomplete operation?

INTRODUCTION: Laparoscopic subtotal cholecystectomy (LSTC) is a bailout procedure that is undertaken when it is not safe to proceed with a laparoscopic total cholecystectomy owing to dense adhesions in Calot's triangle. The main aim of this review was to investigate the early (≤30 days) and late (>30 days) morbidity and mortality of LSTC. METHODS: A literature search of the PubMed® (MEDLINE®), Google Scholar™ and Embase® databases was conducted to identify all studies on LSTC published between 1985 and December 2020. A systematic review was then performed. RESULTS: Overall, 45 studies involving 2,166 subtotal cholecystectomy patients (51% female) were identified for inclusion in the review. The mean patient age was 55 years (standard deviation: 15 years). Just over half (53%) of the patients had an elective procedure. The conversion rate was 6.2% (n=135). The most common indication was acute cholecystitis (49%). Different techniques were used, with the majority having a closed cystic duct/gallbladder stump (71%). The most common closure technique was intracorporeal suturing (53%), followed by endoloop closure (15%). Four patients (0.18%) died within thirty days of surgery. Morbidity within 30 days included bile duct injury (0.23%), bile leak (18%) and intra-abdominal collection (4%). Reoperation was reported in 23 patients (1.2%), most commonly for unresolving intra-abdominal collections and failed endoscopic retrograde cholangiopancreatography to control bile leak. Long-term follow-up was reported in 30 studies, the median follow-up duration being 22 months. Late morbidity included incisional hernias (6%), symptomatic gallstones (4%) and common bile duct stones (2%), with 2% of cases requiring completion of cholecystectomy. CONCLUSIONS: LSTC is an acceptable alternative in patients with a "difficult" Calot's triangle.

Ileostomy formation does not prolong hospital length of stay after open anterior resection when performed within an enhanced recovery programme.

AIM: Previous studies have implicated stoma formation as an independent factor prolonging length of stay (LOS) after colorectal surgery. We examined whether loop ileostomy (LI) formation during an open anterior resection affected LOS within a newly developed enhanced recovery programme (ERP). This involved reorganization of services, including stoma care, to optimize pre- and perioperative patient education, training and expectation, while applying the standard scientific principles of enhanced recovery. METHOD: Data were collected prospectively on 72 consecutive open anterior resections (33 with LI) to see whether LI affected LOS. Stomas were fashioned at the surgeon's discretion and patients were discharged according to agreed criteria. RESULTS: Thirty-three of the 72 patients had a covering LI performed. The overall age range was 32-85 years (median 68), with 40 patients being men. LOS for all 72 patients ranged from 3 to 34 days. The median and mean LOS were the same for both groups (median 6 days, mean 8 days). The complication rate was 44% (32/72) with a leak rate of 7% (5/72) and a mortality of 1.4% (1/72). Between the two groups (no ileostomy vs ileostomy), there was no statistically significant difference in complications (41%vs 48%), leakage (8%vs 6%) and readmission rates (12%vs 5%). CONCLUSION: A covering loop ileostomy need not prolong hospital stay after open anterior resection.

Ablative therapies for colorectal liver metastases: a systematic review.

AIM: The standard treatment for colorectal liver metastases (CRLM) is surgical resection. Only 20-30% of patients are deemed suitable for surgery. Recently, much attention has focused on ablative therapies either to treat unresectable CRLM or to extend the margins of resectability. This review aims to assess the long-term outcome and complication rates of various ablative therapies used in the management of CRLM. METHOD: A literature search was performed of electronic databases including Medline, Cochrane Collaboration Library and the National Library of Medicine's ClinicalTrials.gov. Inclusion criteria were ablation for CRLM with minimum 1 year follow-up and >10 patients, published between January 1994 and January 2010. RESULTS: In all, 226 potentially relevant studies were identified, of which 75 met the inclusion criteria. Cryotherapy (26 studies) had local recurrence rates of 12-39%, with mean 1-, 3- and 5-year survival rates of 84%, 37% and 17%. The major complication rate ranged from 7% to 66%. Microwave ablation (13 studies) had a local recurrence rate of 5-13%, with a mean 1-, 3- and 5-year survival of 73%, 30% and 16%, and a major complication rate ranging from 3% to 16%. Radiofrequency ablation (36 studies) had a local recurrence rate of 10-31%, with a mean 1-, 3- and 5-year survival of 85%, 36% and 24%, with major complication rate ranging from 0% to 33%. CONCLUSION: Ablative therapies offer significantly improved survival compared with palliative chemotherapy alone with 5-year survival rates of 17-24%. Complication rates amongst commonly used techniques are low.

Necrotising enterocolitis in an adult with anorexia nervosa.

Necrotising enterocolitis (NEC) is a rare cause of the acute abdomen in adults and carries one of the highest mortality rates in gastroenterology. However, its rarity confines research to small case reports. Both its pathogenesis and aetiology remain enigmatic in adult patients, proving timely diagnosis and management a challenge. This paper reports on one case of NEC in an adult patient with underlying anorexia nervosa, following a seven-day period of starvation. She underwent emergency laparotomy for resection of necrotic bowel and subsequently made a good recovery. To date, there have only been eight reports linking NEC with anorexia nervosa. We review our patient in the context of plausible mechanisms hypothesised in these cases. Successful management depends on prompt diagnosis, resuscitation and surgical intervention.

Revision using distal inflow for treatment of heart failure secondary to arteriovenous fistula for hemodialysis.

In patients on hemodialysis, cardiovascular disease can be precipitated or worsened by the presence of a high flow arteriovenous fistula. Fistula closure and banding are the traditional treatment methods of dialysis associated high output cardiac failure. We present a case of fistula-related high output cardiac failure treated by revision using distal inflow (RUDI).

Retrospective cohort study of 925 OAGB procedures. The UK MGB/OAGB collaborative group.

BACKGROUND: Mini-One Anastomosis Gastric Bypass is a new operation that provides comparable outcomes to the common bariatric procedures. Revisional surgery is still needed after a number of MGB-OAGB procedures. The aim of this study is to report the causes and management of these revisions. METHODS: From 2010 to 2018, 925 MGB-OAGB operations were performed at 7 bariatric units across the United Kingdom and included in this retrospective cohort study. The data was retrospectively collected and analysed. The primary end point was the identification of the causes and management of revisions. Follow up ranged from 6 months to 3 years. RESULTS: Twenty-two patients [2.3%] required revisional surgery after MGB-OAGB. Five patients [0.5%] developed severe diarrhoea managed by shortening the bilio-pancreatic limb to 150 cm. Four patients [0.4%] developed afferent loop syndrome and bile reflux was reported in another 3 [0.3%] cases; all were managed by either conversion to Roux en Y Gastric Bypass or a Braun anastomosis. Postoperative bleeding was controlled laparoscopically in 3 patients [0.3%]. Liver decompensation that was reported in 2 patients [0.2%] was treated by shortening the BPL in one patient and a reversal to normal anatomy in another. The liver failure resolved in both patients. Other indications for revision included two gastro-jejunal stenosis [0.2%], one perforated ulcer [0.1%], one patient [0.1%] with excessive weight loss and one case [0.1%] of protein malnutrition. None of the 22 patients undergoing revisional surgery after MGB-OAGB died. Lost to follow up rate was 0.2%. CONCLUSION: Complications requiring revisional surgery after MGB-OAGB are uncommon [2.3%] and the majority can be managed by bilio-pancreatic limb shortening, the addition of a Braun side-to-side anastomosis or conversion to RYGB. Bilio-pancreatic limb length of 200 cm or more resulted in serious complications of liver failure, protein malnutrition, excessive weight loss and diarrhoea.

Mini Gastric Bypass: first report of 125 consecutive cases from United Kingdom.

Mini Gastric Bypass is a promising bariatric procedure with multiple apparent benefits. Ours is the first unit within the National Health Service of the United Kingdom to be routinely performing this procedure. This retrospective cohort study reports our experience with first 125 procedures. Data were retrospectively analysed from a prospective database. Information was further supplemented by interviewing team members, contacting patients' general practitioners and telephonic follow-up. The mean follow-up was 11.4 months. There were 86 (68.8%) females and the mean age was 45 (range 20-70) years. Mean weight and body mass index was 135.8 (range 85-244) kilograms and 48.1 (range 34.5-73.8) kg m(-2) , respectively. The mean operating time was 92.4 (range 45-150) minutes and the mean post-operative hospital stay was 2.2 (range 2-17) days. There was no leak, one 30-day reoperation and no mortality in this study. Three patients required late reoperations and four patients developed marginal ulcers. At 6 months follow-up (n = 114), 27.5 (range 11.4-47.4) % total body weight loss and 60.1 (range 23.2-117.5) % excess body weight loss was seen. The figures at 12 months follow-up (n = 65) were 36.8 (range 23.7-55.4) % and 79.5 (range 44.9-138.3) %, respectively. This study demonstrates early safety and efficacy of Mini Gastric Bypass in a carefully selected British obese population in a high-volume centre.

Effect of injectable contraceptives Depo-Provera and norethisterone oenanthate on pituitary gonadotropin response to luteinizing hormone-releasing hormone.

The pituitary response to luteinizing hormone-releasing hormone (LHRH) was tested in women before and approximately 2, 8, and 12 weeks after the injection of either Depo-Provera or norethisterone oenanthate. The secretion of both luteinizing hormone and follicle-stimulating hormone in response to LHRH was similar in the two groups of women, and the pituitary was capable of responding to LHRH at all times studied after injection of the gestagens. There was no statistically significant difference between the response obtained prior to injection and that at any of the other time periods studied after injection.

Comparison of a tumour-derived form of intestinal alkaline phosphatase with foetal and adult intestinal alkaline phosphatases.

An intestinal alkaline phosphatase-like (Kasahara) isoenzyme has been isolated from the serum of a patient with lung cancer and compared with foetal intestinal alkaline phosphatase from the serum of a premature infant and with adult intestinal phosphatase isolated from serum in the same way. Although the ligand-binding sites of the three enzymes were indistinguishable, the foetal intestinal and Kasahara isoenzymes differed slightly from the adult isoenzyme in heat stability and markedly in electrophoretic mobility and neuraminidase-sensitivity, while themselves being similar in these respects. Neither the Kasahara isoenzyme nor foetal phosphatase reacted with anti-placental phosphatase monoclonal antibodies. These results suggest that the Kasahara isoenzyme corresponds to the reappearance of foetal intestinal alkaline phosphatase, rather than to modification of the adult intestinal isoenzyme.

Activity of creatine kinase in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, determined by the "European" recommended method with NAC-EDTA activation.

Creatine kinase activity has been measured at 37 degrees C in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, with activation by N-acetyl cysteine (NAC) and EDTA as recommended by several European committees on standardisation. The upper limit of the reference range for healty women was found to be 170 U/l. The distributions of creatine kinase activities in healthy and carrier women have been used to calculate probability of carrier status as a function of creatine kinase activity. Although the range of creatine kinase activities in normal cord blood is wide, the data provide a basis for interpretation when Duchenne muscular dystrophy is suspected.

Madelung's disease: an uncommon disorder of unknown aetiology?

A case of Madelung's disease (benign multiple symmetrical lipomatosis, Launois-Bensaude syndrome) is described. The characteristic clinical features, associations with chronic alcoholism and a review of the current literature is reported.

Spontaneous resolution of a small extradural haematoma in a child.

We report the rapid spontaneous resolution of a small extradural haematoma (EDH) in a 19-month-old child. The haematoma was managed conservatively. The child went on to make a full recovery. The authors discuss the significance of this surprising clinical finding.

Serum enzymes and bilirubin in neonates after normal or complicated delivery.

318 newborn babies were studied at term and after various complications of pregnancy or delivery for serum total bilirubin, alkaline phosphatase (ALP), asparate aminotransferase (AST), alanine aminotransferase (ALT) and glucose-6-phosphate dehydrogenase (G-6-PD). The total bilirubin levels tended to be lower in infants born after various complications of pregnancy or delivery than at term. The mean activity of ALP in the infants was not different from that of normal adults. Its activity decreased by the 5th day of life and was lower in the fetal distress group. The AST activity was much wider than the adult range but ALT activity did not differ from the adult level.