Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes.

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/- chemoradiation and radical surgery. METHODS: Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. RESULTS: Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. CONCLUSIONS: Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.

The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.

Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960-December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies (n = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy (n = 101) followed by oesophageal adenocarcinoma (OAc, n = 24) and squamous cell carcinoma (OSqCc, n = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers.

Oncological outcomes after pancreatoduodenectomy for pancreatic ductal adenocarcinoma in octogenarians: case-control study.

BACKGROUND: By the end of this decade, 70 per cent of all diagnosed pancreatic ductal adenocarcinomas will be in the elderly. Surgical resection is the only curative option. In the elderly perioperative mortality is higher, while controversy still exists as to whether aggressive treatment offers any survival benefit. This study aimed to assess the oncological benefit of pancreatoduodenectomy in octogenarians with pancreatic ductal adenocarcinoma. METHOD: Retrospective multicentre case-control study of octogenarians and younger controls who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma between 2008 and 2017. The primary endpoint was overall survival and the secondary endpoint was disease-free survival. RESULTS: Overall, 220 patients were included. Although the Charlson co-morbidity index was higher in octogenerians, Eastern Cooperative Oncology Group performance status, ASA and pathological parameters were comparable. Adjuvant therapy was more frequently delivered in the younger group (n = 80, 73 per cent versus n = 58, 53 per cent, P = 0.006). There was no significant difference between octogenarians and controls in overall survival (20 versus 29 months, P = 0.095) or disease-free survival (19 versus 22 months, P = 0.742). On multivariable analysis, age was not an independent predictor of either oncological outcome measured. CONCLUSION: Octogenarians with pancreatic ductal adenocarcinoma of the head and uncinate process may benefit from comparable oncological outcomes to younger patients with surgical treatment. Due to the age- and disease-related frailty and co-morbidities, careful preoperative assessment and patient selection is of paramount importance.

Node negative duodenal adenocarcinoma is associated with long-term patient survival following pancreaticoduodenal resection.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare gastrointestinal malignancy. There is limited data reporting patient outcomes following radical pancreatic resection for DA. We assessed the disease-free (DFS) and overall survival (OS) in patients undergoing pancreaticoduodenectomy for DA in our institution. METHODS: We retrospectively analysed all patients undergoing pancreatic resection of DA at our institution between January 2009 and March 2020 inclusive. RESULTS: Ninteen patients underwent pancreatic resection at our institution for DA during the study period. The overall postoperative morbidity and mortality was 37% and 5%, respectively. Nine patients (47%) had no nodal involvement. Median follow up was 25 months (range 1-108 months). Median DFS for our whole cohort was 17 months but was significantly higher in patients with no nodal metastasis [p < 0.001]. Median OS was 9.5 months for the whole cohort but was significantly higher in the patients with no nodal metastasis (60 months) compared to those with nodal metastasis (17.5 months) [p < 0.003]. CONCLUSION: Improved DFS and OS for patients undergoing pancreaticoduodenectomy for DAs is associated with lymph node negative disease.

Effect of perioperative FLOT versus ECF/ECX on short-term outcomes after surgery for resectable oesophagogastric adenocarcinoma: propensity score-matched study.

BACKGROUND: Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)). METHODS: Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed. RESULTS: Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality. CONCLUSION: In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.

Which surgical strategy for colorectal cancer with synchronous hepatic metastases provides the best outcome? A comparison between primary first, liver first and simultaneous approach.

BACKGROUND: There is no clear consensus about the best surgical strategy for patients with colorectal cancer (CRC) and synchronous liver metastases (SCRLM). METHODS: Between 2009 and 2019, patients with CRC and SCRLM considered for curative treatment were included. Perioperative and follow-up data were analysed to examine the safety and survival outcomes of primary first (PF), liver first (LF) and simultaneous resection (SR) strategies. RESULTS: 204 patients were identified, consisting of PF (n = 129), LF (n = 26) and SR (n = 49). Forty-five patients (22.1%) failed to have either the primary or the liver metastases resected following initial LF (n = 11, 42.3%) or PF (n = 34, 26.4%), respectively (p < 0.001). The postoperative morbidity rates were 31.0%, 38.4% and 40.8% in PF, LF and SR group, respectively (p = 0.409); the mortality rates were 2.3%, 0% and 4.1%, respectively (p = 0.547). The 1-, 3- and 5-year overall survival (OS) were 94%, 72%, 53% in the PF group, 74%, 54%, 36% in the LF group, and 91%, 74%, 63% in the SR group. LF group had the worst OS compared to PF and SR (p = 0.040, p = 0.052). The 1-, 3- and 5-year disease-free survival (DFS) were 31%, 15%, 10% in PF, 21%, 9% and 9% in LF and 45%, 28% and 28% in SR group, respectively. SR group had a better DFS compared to PF and LF (p = 0.005, p = 0.008). At the multivariate analysis, there was no difference between the three strategies in terms of OS (PF vs SR OS-HR 1.090, p = 0.808; LF vs SR OS-HR 1.582, p = 0.365) and the PF had a worse DFS compared to the SR approach (PF vs SR DFS-HR 1.803, p = 0.007; LF vs SR DFS-HR 1.252, p = 0.492). CONCLUSIONS: PF, LF and SR had comparable postoperative morbidity and mortality. The three surgical strategies had similar OS outcomes. The PF strategy was associated with a worse DFS than SR, while the LF approach was associated with a high failure rate to progress to the second stage (primary tumour resection).

Short-term outcomes after pancreatoduodenectomy in octogenarians: multicentre case-control study.

BACKGROUND: Pancreatoduodenectomy (PD) is frequently the surgical treatment indicated for a number of pathologies. Elderly patients may be denied surgery because of concerns over poor perioperative outcomes. The aim of this study was to evaluate postoperative clinical outcomes and provide evidence on current UK practice in the elderly population after PD. METHODS: This was a multicentre retrospective case-control study of octogenarians undergoing PD between January 2008 and December 2017, matched with younger controls from seven specialist centres in the UK. The primary endpoint was 90-day mortality. Secondary endpoints were index admission mortality, postoperative complications, and 30-day readmission rates. RESULTS: In total, 235 octogenarians (median age 81 (range 80-90) years) and 235 controls (age 67 (31-79) years) were included in the study. Eastern Cooperative Oncology Group performance status (median 0 (range 0-3) versus 0 (0-2); P = 0.010) and Charlson Co-morbidity Index score (7 (6-11) versus 5 (2-9); P = 0.001) were higher for octogenarians than controls. Postoperative complication and 30-day readmission rates were comparable. The 90-day mortality rate was higher among octogenarians (9 versus 3 per cent; P = 0.030). Index admission mortality rates were comparable (4 versus 2 per cent; P = 0.160), indicating that the difference in mortality was related to deaths after hospital discharge. Despite the higher 90-day mortality rate in the octogenarian population, multivariable Cox regression analysis did not identify age as an independent predictor of postoperative mortality. CONCLUSION: Despite careful patient selection and comparable index admission mortality, 90-day and, particularly, out-of-hospital mortality rates were higher in octogenarians.

Postoperative day one serum alanine aminotransferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients.

Serum aminotransferases have been used as surrogate markers for liver ischemia-reperfusion injury that follows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postoperative day 1 (POD 1) ALT could be used to predict patient morbidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our institution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient's morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver significantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concurrent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not correlate with patient morbidity after elective liver resection.

Surgery for gallstone disease during pregnancy does not increase fetal or maternal mortality: a meta-analysis.

BACKGROUND: Pregnancy was traditionally considered a contraindication to cholecystectomy but is now becoming the favoured option for gallstone-related disease (GRD) during pregnancy. METHODS: To assess if cholecystectomy during pregnancy increases the risk of preterm labour, fetal mortality and maternal mortality. PubMed and MEDLINE databases for the period from January 1966 through December 2013. Studies were both conservative and surgical intervention was utilised in the management of GRD were included. The results of the included studies were pooled using meta-analysis techniques. RESULTS: Surgical intervention for GRD in pregnancy does not increase the risk of preterm labour, fetal mortality or maternal mortality. CONCLUSIONS: Cholecystectomy during pregnancy for GRD is associated with low complications for the fetus and mother and should be considered in all suitable patients.

Predictors of early recurrence after resection of colorectal liver metastases.

BACKGROUND: Early recurrence after resection of colorectal liver metastases (CLM) is common. Patients at risk of early recurrence may be candidates for enhanced preoperative staging and/or earlier postoperative imaging. The aim of this study was to determine if there are any risk factors that specifically predict early liver-only and systemic recurrence. METHODS: Retrospective analysis of prospective database of patients undergoing liver resection (LR) for CLM from 2004 to 2006 was undertaken. Early recurrence was defined as occurring within 18 months of LR. Patients were classified into three groups: early liver-only recurrence, early systemic recurrence and recurrence-free. Preoperative factors were compared between patients with and without early recurrence. RESULTS: Two hundred and forty-three consecutive patients underwent LR for CLM. Twenty-seven patients (11%) developed early liver-only recurrence. Dukes C stage and male sex were significantly associated with early liver-only recurrence (P < 0.05). Sixty-six patients (27%) developed early systemic recurrence. Tumour size ≥3.6 cm and tumour number (>2) were significantly associated with early systemic recurrence (P < 0.001). CONCLUSIONS: It is possible to stratify patients according to the risk of early liver-only or systemic recurrence after resection of CLM. High-risk patients may be candidates for preoperative MRI and/or computed tomography-positron emission tomography (CT-PET) scan and should receive intensive postoperative surveillance.

Colonic tumour precipitating caecal volvulus within a diaphragmatic hernia.

An 85-year-old woman presented with sudden onset of generalised abdominal pain and absolute constipation for 4 d. On examination she had a distended abdomen. Plain abdominal radiograph revealed a gas filled viscous within the left upper quadrant. Subsequent computed tomography suggested caecal volvulus herniated through a left diaphragmatic hernia. The patient underwent reduction of the internal hernia, right hemicolectomy and mesh repair of the diaphragmatic hernia. Postoperative recovery was uneventful. Histology revealed a Dukes' A colonic cancer within the caecum. Herniation of caecal volvulus through a diaphragmatic hernia is a very rare condition and may have been precipitated by the colonic tumour.

Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation.

Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells or liver resident macrophages with respect to the generation of ROS during IRI. However, little is known about the contribution of endogenous hepatocyte ROS production or its potential impact on the parenchymal cell death associated with IRI and chronic hepatic inflammation. For the first time, we show that human hepatocytes isolated from nondiseased liver tissue and human hepatocytes isolated from diseased liver tissue exhibit marked differences in ROS production in response to hypoxia/reoxygenation (H-R). Furthermore, several different antioxidants are able to abrogate hepatocyte ROS-induced cell death during hypoxia and H-R. These data provide clear evidence that endogenous ROS production by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase drives human hepatocyte apoptosis and necrosis during hypoxia and H-R and may therefore play an important role in any hepatic diseases characterized by a relatively hypoxic liver microenvironment. In conclusion, these data strongly suggest that hepatocytes and hepatocyte-derived ROS are active participants driving hepatic inflammation. These novel findings highlight important functional/metabolic differences between hepatocytes isolated from normal donor livers, hepatocytes isolated from normal resected tissue obtained during surgery for malignant neoplasms, and hepatocytes isolated from livers with end-stage disease. Furthermore, the targeting of hepatocyte ROS generation with antioxidants may offer therapeutic potential for the adjunctive treatment of IRI and chronic inflammatory liver diseases.

Necrotizing black tattoo reaction: what's in a name?

We report the rare case of an 18-year-old man who developed a necrotizing cutaneous reaction 5 days after having a permanent black tattoo on his left forearm spelling his name. Three cases of reactions to permanent black tattoos have been reported within the literature. These cases described the development of cellulitis of the skin adjacent to the tattoo but none reported florid necrotizing cutaneous reactions. The initial management with oral antibacterials failed to resolve the symptoms and use of intravenous antibacterials and topical corticosteroids was needed. Six weeks after presentation the tattoo lettering showed the presence of hyperpigmented skin. Subsequent patch testing confirmed that the patient had no allergy to black tattoo pigments suggesting that the necrotizing cutaneous reaction was secondary to infection. We show that successful treatment of this rare infective complication of permanent black tattoos involves the early institution of intravenous antibacterial agents and topical corticosteroids.

Continued lumbar spinal erosion after repair of chronic contained rupture of a mycotic abdominal aortic aneurysm.

INTRODUCTION: Mycotic aneurysm of the aorta is a rare, dangerous condition. We report a case of an abdominal aortic aneurysm (AAA) caused by Candida albicans. METHODS: Case report and review of pertinent English-language literature. CASE REPORT: A 48 year-old man presented with an acute exacerbation of long-standing back pain. Examination revealed a pulsatile epigastric mass, and radiologic examinations confirmed a 9 cm chronic contained rupture of an inflammatory infrarenal AAA. At operation, no posterior aneurysm sac was found, and lumbar vertebral erosion was noted. Lower limb vascularity was secured with left axillo-bifemoral bypass. The patient presented 12 months later with severe non-mechanical back pain. Imaging confirmed continuing vertebral erosion. At laparotomy, an autologous fibula strut was used for spinal stabilization. CONCLUSION: Aggressive multimodality therapy of infected AAA and associated vertebral osteomyelitis is necessary for a successful outcome.

Late presentation of an infected carotid patch as a superficial wound nodule.

BACKGROUND: Infection of a vascular patch is an uncommon complication of carotid endarterectomy. METHODS: Case report and review of the pertinent English-language literature. CASE REPORT: A 71 year-old woman with a carotid patch infection presented with a superficial wound nodule and no false aneurysm. Diagnosis thus was delayed but was confirmed eventually with magnetic resonance imaging. Excision and saphenous vein bypass was successful. CONCLUSION: The rare complication of infection of a polyester vascular patch is described with recommendations for early diagnosis and definitive therapy.

Bilateral synchronous ductal carcinoma in situ in a young man: case report and review of the literature.

We report a rare case of synchronous bilateral ductal carcinoma in situ (DCIS) developing in a man with long-standing gynecomastia. He underwent bilateral staged subcutaneous mastectomies with the right side being performed first at age 26 years. Histology confirmed bilateral pure DCIS. There was no identifiable causative factor for the development of bilateral DCIS, and there was no familial history of the disease. He ultimately experienced progression to total bilateral mastectomies. This case highlights the importance of remaining vigilant about the presence of malignancy in normally benign conditions.