Donal Maguire

A prospective study of common bile duct calculi in patients undergoing laparoscopic cholecystectomy: Natural history of choledocholithiasis revisited

Objective:To define the incidence of problematic common bile duct calculi in patients undergoing laparoscopic cholecystectomy. Summary Background Data:In patients selected for laparoscopic cholecystectomy, the true incidence of potentially problematic common bile duct calculi and their natural history has not been determined. We evaluated the incidence and early natural history of common bile duct calculi in all patients undergoing laparoscopic cholecystectomy with intraoperative and delayed postoperative cholangiography. Methods:Operative cholangiography was attempted in all patients. In those patients in whom a filling defect was noted in the bile duct, the fine bore cholangiogram catheter was left securely clipped in the cystic duct for repeated cholangiography at 48 hours and at approximately 6 weeks postoperatively. Results:Operative cholangiography was attempted in 997 consecutive patients and was accomplished in 962 patients (96%). Forty-six patients (4.6%) had at least one filling defect. Twelve of these had a normal cholangiogram at 48 hours (26% possible false-positive operative cholangiogram) and a further 12 at 6 weeks (26% spontaneous passage of calculi). Spontaneous passage was not determined by either the number or size of calculi or by the diameter of the bile duct. Only 22 patients (2.2% of total population) had persistent common bile duct calculi at 6 weeks after laparoscopic cholecystectomy and retrieved by endoscopic retrograde cholangiopancreatography. Conclusions:Choledocholithiasis occurs in 3.4% of patients undergoing laparoscopic cholecystectomy but more than one third of these pass the calculi spontaneously within 6 weeks of operation and may be spared endoscopic retrograde cholangiopancreatography. Treatment decisions based on assessment by operative cholangiography alone would result in unnecessary interventions in 50% of patients who had either false positive studies or subsequently passed the calculi. These data support a short-term expectant approach in the management of clinically silent choledocholithiasis in patients selected for LC.

Rapid responses to aldosterone in human distal colon

Aldosterone at normal physiological levels induces rapid increases in intracellular calcium and pH in human distal colon. The end target of these rapid signaling responses are basolateral K+ channels. Using spectrofluorescence microscopy and Ussing chamber techniques, we have shown that aldosterone activates basolateral Na/H exchange via a protein kinase C and calcium-dependent signaling pathway. The resultant intracellular alkalinization up-regulates an adenosine triphosphate (ATP)-dependent K+ channel (K(ATP)) and inhibits a Ca2+ -dependent K+ channel (K(Ca)). In Ussing chamber experiments, we have shown that the K(ATP) channel is required to drive sodium absorption, whereas the K(Ca) channel is necessary for both cyclic adenosine monophosphate and calcium-dependent chloride secretion. The rapid effects of aldosterone on intracellular calcium, pH, protein kinase C and K(ATP), K(Ca) channels are insensitive to cycloheximide, actinomycin D, and spironalactone, indicating a nongenomic mechanism of action. We propose that the physiological role for the rapid nongenomic effect of aldosterone is to prime pluripotential epithelia for absorption by simultaneously up-regulating K(ATP) channels to drive absorption through surface cells and down-regulating the secretory capacity by inhibiting K(Ca) channels involved in secretion through crypt cells.

Bone marrow micrometastases and gastrointestinal cancer detection and significance

Accurate staging of cancer is important, as the presence or absence of systemic spread determines treatment. The sensitivity of current imaging and biochemical techniques is suboptimal for the detection of minimal residual disease and latent metastases. This results in understaging and potential undertreatment. To improve detection of disseminated epithelial malignancy, immunohistochemical and molecular methods have been employed that search for epithelial cell–specific proteins in nonepithelial tissue. Bone marrow is mesenchymal tissue (that does not normally express epithelial cell components) and represents an accessible window for detection of micrometastatic carcinoma cells. Detection methods for epithelial cell components (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen) include immunohistochemistry, flow cytometry, reverse transcriptase polymerase chain reaction (rt-PCR), and enzyme linked immunoassay (ELISA). Micrometastatic cells in bone marrow are viable, capable of proliferation, resistant to immune attack, and insensitive to s-phase chemotherapeutic agents. Patients with carcinomas of the lung, breast, prostate, or gastrointestinal tract and in whom bone marrow micrometastases are detected have a foreshortened interval to recurrence and impaired survival. Detection of micrometastases deserves serious consideration in treatment protocols, and standardization of methods is now required.

Detection and clinical significance of bone marrow micrometastases in patients undergoing liver transplantation for hepatocellular carcinoma

Background. Existing methods of selecting patients with hepatocellular carcinoma (HCC) for liver transplantation rely on computed tomography and magnetic resonance imaging, which fail to detect vascular invasion or micrometastases. Vascular invasion cannot be assessed pretransplant because of the risks of tumor biopsy. Pretransplant detection of micrometastases in bone marrow is an alternative method that may identify patients at risk of recurrence and permit better organ allocation. The authors’ aim was to develop an accurate method of detecting hepatocellular carcinoma micrometastases that may have a clinical role in pretransplant assessment. Methods. Iliac crest bone marrow was sampled from 18 patients with HCC (before liver transplantation) and 14 controls (cirrhosis, 9; hematologic disorders, 5). Mononuclear bone marrow fractions were evaluated for the presence of micrometastases by immunocytochemistry (ICC) using Hep Par-1 (HPICC) and Glypican-3 (GPICC), and by reverse-transcriptase (RT) polymerase chain reaction using two primer pairs targeting albumin (Alb1RT and Alb2RT) and one pair targeting &agr;-fetoprotein (AFPRT). Each marker was compared in terms of (1) specificity and (2) positive and negative predictive values for tumor recurrence. Results. The specificity of each marker for detecting HCC micrometastases were as follows: HPICC, 93%; GPICC, 92%; Alb1RT, 33%; Alb2RT, 59%; and AFPRT, 0%. The positive (negative) predictive values for HPICC, GPICC, and Alb2RT for posttransplant tumor recurrence were 42% (100%), 40% (73%), and 0% (43%), respectively. HPICC-positive micrometastases were identified in all patients with postoperative tumor recurrence (n=5) and in 75% of patients with microscopic vascular invasion. Conclusions. Detection of HCC micrometastases in bone marrow of potential liver transplant candidates is a potentially useful technique that may provide important prognostic information without the need for preoperative tumor biopsy. The authors’ preliminary data indicate that HPICC is a promising immunocytochemical marker for HCC micrometastases, and larger studies are needed to confirm its clinical role.

Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis

Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. Methods: From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. Results: Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. Conclusion: In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to surgery with comparable morbidity and mortality rates to isolated hepatectomy.

Perioperative outcomes of laparoscopic total extraperitoneal inguinal hernia repair

Background: Laparoscopic total extraperitoneal (TEP) inguinal hernia repair has become increasingly common over the past decade due to reported reduced postoperative pain, shorter convalescence and lower incidence of long-term surgical related morbidity such as chronic pain and numbness. However, the technique has not yet become standard of care in many institutions. The hesitation to adopt this approach may be related to the relatively long learning curve and limited high quality outcome data available. The purpose of this study was to evaluate perioperative morbidity and short-term outcomes of laparoscopic TEP repair. n Methods: We performed a retrospective review of a consecutive series of patients who underwent laparoscopic TEP inguinal hernia repair over a 10-year period. Data collected included patient demographics, operative parameters and postoperative complications. n Results: A total of 403 patients underwent laparoscopic TEP repair for the management of unilateral or bilateral inguinal hernia. The median age was 51 and 97% were males. The median BMI was 26 and 96% were ASA grade 1 or 2. Ninety-seven percent of repairs were primary, 15% were bilateral and 65% were indirect. The mean operative duration was 50 minutes over the entire study period, however this decreased significantly with time to a mean of 37 minutes in the final year. Postoperative complications occurred in 10.6%, 86% were Clavien-Dindo grade 1 and there were no significant visceral or vascular injuries. The most common complications were seroma formation (4.2%), urinary retention (3.7%) and rectus sheath haematoma (1.4%). Almost all patients were discharged within 24 hours. n Conclusions: Laparoscopic TEP repair is a safe and well tolerated surgical treatment of inguinal hernia, associated with a low incidence of perioperative complications.

Diagnosis and Implications of Bone Marrow Micrometastases

At presentation cancer is a systemic disease in the majority of patients with malignancy of the esophagus and stomach. This dissemination is represented by either isolated or microaggregates of tumor cells, which have the potential to establish overt metastases, and are not detectable by serological measurements of tumor markers or by radiological imaging. These micrometastases are present in approximately 90% of patients who are subjected to curative excisional surgery and explain the frequent early tumor recurrences after radical resection. At diagnosis, the clinico-pathological stage of primary cancer remains the best predictor of outcome and is the determinant of treatment strategy1–3. When disseminated disease is present, cure by excision of the primary is not possible unless effective adjuvant therapies are available.