Open and Minimal Approaches to Pancreatic Adenocarcinoma.

Surgical options and approaches to pancreatic cancer are changing in the current era. Neoadjuvant treatment strategies for pancreatic cancer combined with the increased use of minimal access surgical techniques mean that the modern pancreatic surgeon requires mastering a number of surgical approaches with to optimally manage patients. Whilst traditional open surgery remains the most frequent approach for surgery, the specific steps during surgery may need to be modified in light of the aforementioned neoadjuvant treatments. Robotic and laparoscopic approaches to pancreatic resection are feasible, but these surgical methods remain in their infancy. In this review article, we summarise the current surgical approaches to pancreatic cancer and how these are adapted to the minimal access setting with discussion of the patient outcome data.

Pancreatic tail splenunculus: Case report and review of the literature.

INTRODUCTION: Mass lesions in the pancreatic tail are increasingly identified upon radiological imaging. However the diagnosis of these lesions can be challenging and impact significantly upon patient management. PRESENTATION OF CASE: We report a case of an intrapancreatic accessory spleen initially diagnosed as a neuroendocrine tumour of the pancreas tail following nuclear scintigraphy. DISCUSSION: The investigation of solitary pancreatic tail lesions and the potential management paradigms are discussed. CONCLUSION: Solitary lesions within the pancreatic tail should have splenunculus included in the differential diagnosis.

Increased carcinoembryonic antigen (CEA) following neoadjuvant chemotherapy predicts poor prognosis in patients that undergo hepatectomy for liver-only colorectal metastases.

BACKGROUND: The importance of preoperative chemotherapy in a multimodality management of patients with colorectal liver metastases (CRLM) has been demonstrated. We analyse the carcinoembryonic antigen (CEA) changes following neoadjuvant chemotherapy in patients with CRLM who underwent liver resection. METHODS: The final cohort included 107 eligible patients. Increased CEA levels following neoadjuvant chemotherapy were defined as the increase of baseline CEA level at diagnosis of CRLM compared with the CEA level after completion of neoadjuvant chemotherapy. Disease-free survival (DFS), post-recurrence survival (PRS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Cox-regression methods. RESULTS: CEA increase was associated with decreased PRS and OS (HR 2.69; 95 % CI, 1.28-5.63; p = 0.009, and HR 2.50; 95 % CI, 1.12-5.56; p = 0.025, respectively) in multivariate analysis, but there was no association between CEA changes and DFS. CEA increase was only associated with disease progression during preoperative chemotherapy (p = 0.014). Interestingly, this association was not absolute, as only 5 of the 11 patients with disease progression demonstrated CEA increase. Regarding the remaining 12 patients with CEA increase, according to RECIST criteria, eight patients demonstrated partial response and four patients stable disease. CONCLUSION: In this study, we demonstrated the CEA increase following neoadjuvant chemotherapy as an adverse prognostic factor for PRS, and OS but not for DFS in patients undergoing liver resection for liver-only colorectal metastases.

The Preoperative Lymphocyte-to-Monocyte Ratio is Prognostic of Clinical Outcomes for Patients with Liver-Only Colorectal Metastases in the Neoadjuvant Setting.

BACKGROUND: Circulating monocyte-derived, tumor-associated macrophages are associated with a poor prognosis for various cancers. Conversely, circulating lymphocytes are the source of tumor-infiltrating lymphocytes, which are associated with an improved prognosis. This study evaluated the prognostic value of the preoperative blood lymphocyte-to-monocyte ratio (LMR) for patients undergoing hepatectomy for liver-only colorectal metastases. METHODS: This retrospective study examined 140 consecutive patients with liver-only colorectal metastases. Disease-free survival (DFS), post-recurrence survival (PRS), cancer-specific survival (CSS), and overall survival (OS) were analyzed in relation to LMR values using both Kaplan-Meier and multivariate Cox-regression methods. RESULTS: In the multivariate analysis, high LMR (>3) was significantly associated with increased OS [hazard ratio (HR), 2.43; 95 % confidence interval (CI), 1.32-4.48; P = 0.004], CSS (HR 2.15; 95 % CI 1.13-4.10; P = 0.020), and PRS (HR 2.15; 95 % CI 1.15-4.01; P = 0.016) but not with DFS. An LMR lower than 3 may have been associated with decreased CSS and PRS by increasing the rate of multifocal recurrence (P = 0.063). In the multivariate analysis comparing LMR, the neutrophil-lymphocyte ratio, and the platelet-lymphocyte ratio, LMR remained the only significant prognostic variable of CSS. CONCLUSION: This study identified preoperative LMR as an independent prognostic factor for PRS, CSS, and OS but not for DFS in patients undergoing hepatectomy for liver-only colorectal metastases. In the future, interventions to augment immune function could improve survival for low-LMR patients.

PEComa in a Young Patient with Known Li-Fraumeni Syndrome.

Perivascular epithelioid cells neoplasms (PEComas) constitute a family of rare tumours which have been reported virtually in all anatomic sites. The histological clarification of the malignant potential of these tumours is still problematic despite the proposed risk stratification systems. Li-Fraumeni syndrome (LFS) is caused by a germline mutation in the TP53 tumour suppressor gene. It is a rare but well-characterized cancer predisposition syndrome leading to the development of a variety of different tumour types. To the best of our knowledge, an association between this syndrome and PEComas has not been previously documented. A 24-year-old lady with known LFS presented with two uncertain-in-nature lesions, one within the right part of the liver and one within the upper pole of the right kidney. The patient underwent an uncomplicated open simultaneous right partial nephrectomy and resection of segment 7 of the liver. The morphological and immunohistochemical features of both lesions were of epithelioid angiomyolipoma (PEComa). Although the obvious scenario was that the liver lesion was a metastasis from the renal lesion, the assessment of their malignant potential according to the existing risk stratification systems was rather in favour of two synchronous primary PEComas, pointing out that the histological assessment of malignant potential of PEComas is still problematic.

Neutrophil to lymphocyte ratio predicts pattern of recurrence in patients undergoing liver resection for colorectal liver metastasis and thus the overall survival.

OBJECTIVE: We investigate the neutrophil to lymphocyte ratio (NLR) as a potential prognostic factor for patients undergoing curative liver resection for colorectal liver metastasis (CRLM). METHODS: We identified patients who underwent liver resection, via our prospectively accumulated surgical database at the Royal Marsden Hospital and The London Clinic, by two liver surgeons (SM and AZK) between January 2005 and December 2012 and patients included had liver resection for CRLM and received preoperative chemotherapy with an NLR > 2.5 considered elevated. NLR's role in disease-free, post-recurrence and overall survival was determined by univariate and multivariate Cox regression models. RESULTS: One hundred and sixty nine patients were enrolled. Seventy-one patients (42%) demonstrated NLR > 2.5. Elevated NLR was associated with decreased OS in univariate and multivariate analysis (HR 2.12; 95% CI, 1.18-3.82; P = 0.012) but not with DFS. Analyzed as continuous variable, higher NLR was associated with decreased OS(HR 1.17; 95% CI, 1.03-132; P = 0.011) and associated with increased risk of extrahepatic/multifocal recurrence (P = 0.007), linked in this way with a decreased post-recurrence survival (HR 1.24, 95% CI, 1.02-1.52; P = 0.032). CONCLUSIONS: Elevated NLR in patients who undergo hepatectomy following neoadjuvant chemotherapy for CRLM increases risk of extrahepatic/multifocal recurrence and is an independent predictor of overall survival.

Pancreatic perivascular epithelioid cell tumour presenting with upper gastrointestinal bleeding.

PEComa is a family of rare mesenchymal tumours which can occur in any part of the human body. Primary PEComas of the pancreas are extremely rare tumours with uncertain malignant potential. A 17-year-old female was admitted to the hospital due to melena. She required several transfusions. CT scan demonstrated a mass at the head of the pancreas measuring 4.2 cm in maximum diameter. An endoscopic ultrasound showed an ulcerating malignant looking mass infiltrating 50% of the wall of the second part of the duodenum in the region of the ampulla. Multiple biopsies taken showed extensive ulceration with granulation tissue formation and underlying large macrophages without being able to establish a definite diagnosis. We proceeded with pylorus-preserving pancreaticoduodenectomy. The postoperative course of the patient was unremarkable, and she was discharged on the 8th postoperative day. Histology examination of the specimen showed a PEComa of pancreas. Eighteen months after resection the patient is disease free. To the best of our knowledge this is the first time we describe a case of a pancreatic PEComa presenting with massive gastrointestinal bleeding.

Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor.

Recent evidence indicates that inflammation is an essential component of pathogenesis and progression of cancer. In this study, we analysed two indexes of systemic inflammation, the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), with disease-free survival (DFS) and overall survival (OS) in liver-only colorectal metastases treated with liver resection following neoadjuvant chemotherapy. In this retrospective study, 140 patients were enroled. The NLR and PLR were calculated on the basis of preoperative blood cell count, and their cut-off levels were determined by applying receiver operating curve analysis. A NLR>2.4 and a PLR>150 were considered to be elevated. DFS and OS were calculated using both Kaplan-Meier and multivariate Cox regression methods. Both high NLR and high PLR were associated with decreased DFS [HR 1.55; 95% confidence interval (CI) 1.03-2.32; P=0.033, and HR 1.78; 95% CI 1.19-2.67; P=0.005, respectively] and OS (HR 2.21; 95% CI 1.24-3.96; P=0.007, and HR 2.90; 95% CI 1.61-5.21; P<0.001, respectively) in univariate analysis, but only PLR remained significant in multivariate analysis for both DFS and OS (HR 1.68; 95% CI 1.04-2.71; P=0.034, and HR 2.17; 95% CI 1.09-4.32; P=0.027, respectively). When we divided patients into three groups (group 1: normal both NLR and PLR; group 2: high NLR or high PLR; group 3: high both NLR and PLR), the five-year DFS and OS rates for these groups were 43, 26, 9% (P=0.004) and 73, 59, 34% (P<0.001), respectively. In this study, we indicate that preoperative PLR is superior to preoperative NLR as an adverse prognostic factor in patients who undergo liver resection for liver-only colorectal metastases.

Correlation between postoperative infective complications and long-term outcomes after hepatic resection for colorectal liver metastasis.

BACKGROUND: The impact of postoperative morbidity, and in particular infective complications on long-term outcomes, following hepatic resection for colorectal liver metastasis (CRLM) is not widely published. OBJECTIVE: To evaluate the effect of postoperative complications on disease recurrence and overall survival in patients undergoing hepatic resection for CRLM. METHODS: All patients undergoing hepatic resection for CRLM from January 1993 and March 2007 were identified, and postoperative complications analyzed. Patients who died of postoperative complications within 30 days of surgery were excluded form the study. Postoperative complications were graded using a validated system of classification. Complications were further classified into infective and noninfective complication groups and the primary end points of the study were disease free survival (DFS) and overall survival (OS) at 5 years. RESULT: A total of 705 patients underwent hepatic resection in the study period. Median follow-up was 38 months. Operative morbidity and mortality were 28% and 3.6%, respectively. The total number of patients was 197 (28%) with complications, and 508 (72%) without complications. The 5 year DFS and OS for those with and without complications were: 13% versus 26% (P < 0.001) and 24% versus 37% (P < 0.001), respectively. Multivariate analysis showed inflammatory response to tumor score, blood transfusion, tumor number >8, and postoperative sepsis to be independent factors associated with DFS, and inflammatory response to tumor, tumor number >8, and postoperative sepsis to be independent predictors for OS. Intra-abdominal and respiratory infection but not wound infections were associated with poorer long-term outcomes. CONCLUSIONS: Postoperative complications influence long-term outcomes in hepatic resection for CRLM. Specifically, postoperative sepsis is an independent predictor of disease free and overall survival. Thorough preoperative optimization, meticulous surgical technique and careful management in the postoperative period may reduce the incidence of these complications and influence long-term outcomes.

Laparoscopic left lateral sectionectomy: surgical technique and our results from Leeds.

BACKGROUND: Although laparoscopic left lateral sectionectomy is increasingly becoming the accepted approach for resection of tumors in hepatic segments II and III, the variations in surgical technique exist. METHODS: Our technique relies on mobilization of the left lateral sector followed by extracorporeal control of the portal pedicle allowing intermittent occlusion when needed. The parenchyma is thinned, exposing the inflow and outflow allowing application of endoscopic staplers under direct vision for parenchymal transection. RESULTS: Eleven patients underwent left lateral sectionectomy between 2000 and November 2007 and had a median postoperative stay of 3 days. Two patients had to be converted early on. CONCLUSION: Left lateral sectionectomy using this approach appears to be safe and reproducible, and this technique should be considered for patients with tumors in hepatic segments II and III.

Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases.

BACKGROUND AND AIMS: Neoadjuvant chemotherapy is increasingly being used to enlarge the cohort of patients who can be offered hepatic resection for malignancy. However, the impact of these agents on the liver parenchyma itself, and their effects on clinical outcomes following hepatic resection remain unclear. This review identifies patterns of regimen-specific chemotherapy-induced hepatic injury and assesses their impact on outcomes following hepatic resection for colorectal liver metastases (CLM). METHODS: An electronic search was performed using the MEDLINE (US Library of Congress) database from 1966 to May 2007 to identify relevant articles related to chemotherapy-induced hepatic injury and subsequent outcome following hepatic resection. RESULTS: The use of the combination of 5-flourouracil and leucovorin is linked to the development of hepatic steatosis, and translates into increased postoperative infection rates. A form of non-alcoholic steatohepatitis (NASH) related to chemotherapy and otherwise known as chemotherapy-associated steatohepatitis (CASH) is closely linked to irinotecan-based therapy and is associated with inferior outcomes following hepatic surgery mainly due to hepatic insufficiency and poor regeneration. Data on sinusoidal obstruction syndrome (SOS) following treatment with oxaliplatin are less convincing, but there appears to be an increased risk for intra-operative bleeding and decreased hepatic reserve associated with the presence of SOS. Intra-arterial floxuridine therapy damages the extrahepatic biliary tree in addition to causing parenchymal liver damage, and has been shown to be associated with increased morbidity after hepatic resection. CONCLUSION: Agent-specific patterns of damage are now being recognized with increasing use of neoadjuvant chemotherapy prior to surgery. The potential benefits and risks of these should be considered on an individual patient basis prior to hepatic resection.

Double gallstone ileus.

BACKGROUND: Gallstone ileus remains a rare but important cause of intestinal obstruction. METHOD: We present a unique case of two gallstones causing intestinal obstruction at the same time. RESULTS: A 90-year-old lady presented with signs and symptoms of small bowel obstruction. At operation, two gallstones stuck at different points within the bowel were causing the obstruction and were removed. CONCLUSION: When operating on patients with small bowel obstruction from gallstone ileus, examination of the entire small bowel should be considered mandatory.

Vomiting-induced pneumomediastinum and subcutaneous emphysema does not always indicate Boerhaave's syndrome: report of six cases.

Spontaneous pneumomediastinum is an uncommon, self-limiting condition resulting from alveolar rupture in young adults. Because of the ambiguous presentation and the general lack of awareness of this condition, its diagnosis is often delayed, missed, or confused with spontaneous esophageal perforation. We report our experience of treating six patients who were referred to our unit with vomiting-induced pneumomediastinum, subcutaneous emphysema, and an initial diagnosis of spontaneous esophageal perforation. Ultimately, we diagnosed spontaneous pneumomediastinum in all six patients, who recovered uneventfully without any surgical intervention. We review the literature with particular emphasis on differentiating spontaneous pneumomediastinum from spontaneous esophageal perforation.

Transabdominal approach for management of Boerhaave's syndrome.

Several transthoracic approaches have been described for the surgical management of Boerhaave's syndrome that carry their own morbidity in patients who can be systemically unwell at presentation, and best practice is not established. We introduce a novel transabdominal approach to manage the perforation and spare these patients the trauma of a thoracotomy. Four patients with spontaneous esophageal rupture were managed using a transabdominal approach. Postoperative complications, length of intensive care unit stay, postoperative hospital stay, time to oral intake, and morbidity and mortality were used as outcome measures. After operation, the median intensive care unit stay was 4 days (range, 0-5) in patients who required a median of 10.5 days (range, 6-17) to establish oral intake. One patient required a transthoracic drainage of an empyema and one patient required percutaneous drainage of a mediastinal collection. The median length of stay was 38 days and there was zero mortality. The transabdominal approach is safe and effective for the management of Boerhaave's syndrome and should be considered in the treatment paradigm for this condition. Intrathoracic complications account for postoperative morbidity.

Liver regeneration: mechanisms, mysteries and more.

BACKGROUND: Liver regeneration remains a fascinating topic, still partly clouded to many as to the exact cellular and molecular mechanisms that bring about this phenomenon. It is an area, therefore, of active research today. This review looks at the recent published reports that have led to a greater understanding of this process. METHODS: A database search was carried out on Medline search using the terms liver regeneration with no linguistic limitations from 1966 to 2006. RESULTS: There are two randomized controlled trials on the topic and most data and information have come from experimental studies in animals. CONCLUSION: Liver regeneration is a complex, tightly controlled process involving many inflammatory cells growth factors and hormones. More information about it is awaited in studies on humans.