Mayank Bhandari

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion

BACKGROUND Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin <or=2 mm (P < 0.02), nodal involvement (P < 0.003), perineural infiltration (P < 0.0001) and lymphovascular invasion (P < 0.002) were associated with poorer prognosis. In a multivariate analysis, histologically identified perineural infiltration (P < 0.03) and lymphovascular invasion (P= 0.05) were significant factors influencing outcome. Five-year survival was 77% in patients negative for both factors and 15% in patients positive for both (P < 0.0001). In the pancreatic adenocarcinoma subgroup, patients who were negative for both factors had a 5-year survival of 71%, whereas those who were positive for both had a 5-year survival of 16% (P < 0.02). CONCLUSIONS The presence of perineural infiltration and lymphovascular invasion on histopathology is highly significant in predicting 5-year outcomes after pancreaticoduodenectomy for periampullary and pancreatic malignancies.

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

Objectives: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP. Methods: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis. Results: Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating. Conclusions: These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

Galanin in the regulation of pancreatic vascular perfusion

Objectives: Acute pancreatitis is associated with compromised pancreatic microcirculation. Galanin is a vasoactive neuropeptide, but its role in the regulation of pancreatic vascular perfusion (PVP) is unclear. Methods: Localization of galanin immunoreactivity was investigated by immunohistochemistry, and the effects of bolus doses of galanin or the antagonist galantide on blood pressure (BP) and PVP (by laser Doppler fluxmetry) were determined in anesthetized possums. Results: Galanin immunoreactivity was abundant in the possum pancreas particularly around blood vessels. Galanin (0.001-10 nmol) produced a dose-dependent increase in BP (to 177% of baseline) and a complex PVP response consisting of a transient increase, then a fall below baseline with recovery to above baseline. Galantide (0.003-30 nmol) caused a dose-dependent biphasic response in BP, with a reduction, recovery, then a further fall, followed by recovery, whereas PVP increased (178%) then fell (to 56%) of baseline. Similar effects were produced by continuous intravenous infusion of galanin (1 and 10 nmol) or galantide (3 and 30 nmol). The second-phase response of these agents is probably a passive response of the pancreatic vasculature to systemic cardiovascular effects. Conclusions: These data suggest that galanin acutely reduces PVP, whereas galantide increases it, implying galanin may be important in the regulation of PVP.

Preoperative biliary drainage (stenting) for treatment of obstructive jaundice

The role of preoperative biliary drainage in malignant obstructive jaundice has been controversial. Laboratory studies suggest that relief of jaundice prior to major pancreatic resection would be associated with improved morbidity and mortality. However, clinical experience has not supported the laboratory results. Obstructive jaundice can be relieved preoperatively via an endoprosthesis introduced either percutaneously or endoscopically. Cohort studies have not shown any clinical benefit and in some the endoprostheses have been implicated in postoperative complications. The only randomized study has shown no benefit in preoperative drainage, but one recent study has confirmed that endoscopic drainage, whilst not conferring an advantage, did no harm. Hence, whilst preoperative drainage is not recommended, if for any reason operation needs to be delayed, endoscopic drainage via an endoprosthesis can be used without fear of adversely influencing the outcome.

Caecal Herniation through the Foramen of Winslow

Internal hernia is the protrusion of an abdominal viscus through the peritoneum or mesentery into a compartment within the abdominal cavity. We present a case of internal herniation through the foramen of Winslow that was identified by CT imaging. It was treated with reduction at laparotomy and subsequent right hemicolectomy. SUMMARY Internal hernia refers to the protrusion of an abdominal viscus through the peritoneum or mesentery into a compartment within the abdominal cavity and represents an uncommon cause of bowel obstruction. Six main types of internal herniation have been described, which are paraduodenal, foramen of Winslow, transmesenteric, paracaecal, intersigmoid and paravesical. Of these, protrusion through the foramen of Winslow is rare and accounts only for approximately 8% of all internal herniae. Various organs have hitherto been found to herniate through this foramen. Here, we report a case of caecal herniation that was only diagnosed by a CT scan. CLINICAL PRESENTATION A 57-year-old male presented with a 1-day history of sudden onset epigastric and chest pain, associated with nausea, coffee ground vomiting and rectal bleeding. On systemic enquiry of the gastrointestinal system, there was no history of abdominal distension and the patient reported bowel opening the day prior to admission. He had no past history of abdominal surgery but suffered from Type 2 diabetes mellitus and learning difficulties. Clinical examination revealed mild epigastric tenderness in the absence of guarding and rigidity, but was accompanied by reduced bowel sounds, with no evidence of inguinal or femoral herniation. On admission, he was apyrexial and results of blood test showed an increased white cell count (16.1, normal range 4–11 10 l), amylase (279, normal range 30–123U l) and alanine transaminase (60, normal range 9–55U l), as well as deranged renal function tests (creatinine, 151, normal range 36–107mmol l; urea, 15.5, normal range 2.5–7.8mmol l). Erect chest and abdominal radiography demonstrated gas collection under the hemidiaphragm within a bowel loop but no free air, as well as a distended stomach. The patient was admitted under the medical team with a differential diagnosis of acute coronary syndrome, but his electrocardiogram and troponin were unremarkable. A surgical opinion was therefore requested. An urgent CT scan of the abdomen and pelvis demonstrated large pockets of gas and faeces in the left hypochondrium adjacent to the stomach. This was suggestive of an abnormally lying caecum, secondary to either internal herniation or a volvulus. There was no evidence of free gas in the abdomen. Figure 1 shows a coronal section of the CT scan. Here, the stomach (S) is lying below the left hemidiaphragm with the caecum (C) below it and passing through the foramen of Winslow. An axial view is shown in Figure 2, where the caecum is located behind the stomach. The patient underwent urgent laparotomy that confirmed an internal hernia of the caecum through the foramen of Winslow, lying behind the stomach in the lesser sac causing small bowel obstruction. The caecum showed evidence of ischaemia and necrosis, but there was no abdominal contamination (Figure 3). During surgery, after gaining access via the lesser sac, the caecum was decompressed and subsequently reduced through the foramen. A right hemicolectomy was performed with a side-to-side stapled anastomosis. Postoperatively, the patient was transferred to the high dependency unit, went on to have an uneventful recovery and was discharged home a week later. DISCUSSION Internal hernia refers to the protrusion of an abdominal viscus through the peritoneum or mesentery into a compartment within the abdominal cavity. It is an uncommon cause of small bowel obstruction, accounting for around 5% of all cases. Timely diagnosis is crucial because BJR|case reports http://dx.doi.org/10.1259/bjrcr.20150330

Influence of primary site on metastatic distribution and survival in stage IV colorectal cancer

To assess pattern distribution and prognosis of the three anatomical entities of metastatic colorectal cancer, and influence of treatment of metastases on survival.