Stephan Timm

Achalasia—If Surgical Treatment Fails: Analysis of Remedial Surgery

IntroductionHeller myotomy leads to good–excellent long-term results in 90% of patients with achalasia and thereby has evolved to the “first-line” therapy. Failure of surgical treatment, however, remains an urgent problem which has been discussed controversially recently.Materials and MethodsA systematic review of the literature was performed to analyze the long-term results of failures after Heller’s operation with emphasis on treatment by remedial myotomy.DiscussionOther reinterventions and their causes after failure of surgical treatment in patients with achalasia are discussed.

Territorial belonging of the middle hepatic vein in living liver donor candidates evaluated by three-dimensional computed tomographic reconstruction and virtual liver resection.

Postoperative venous congestion can lead to graft and remnant liver failure in living donor liver transplantation. This study was designed to delineate ‘territorial belonging’ of the middle hepatic vein (MHV) and to identify hepatic venous anatomy at high risk of outflow congestion.

Technische Aspekte der laparoskopischen Heller-Myotomie bei der Achalasie

Minimally invasive surgery has influenced the treatment of achalasia more than that of any other gastrointestinal disorder. Laparoscopic Heller myotomy has thus evolved to the first-line therapy in patients with achalasia and led to a significant change in the treatment algorithm of this disorder. The aim of this article is to present technical aspects and pitfalls of Heller myotomy with combined antirefluxplasty. After injection of 0.9% NaCl into the muscularis and submucosa of the distal esophagus and proximal fundus, whereby the submucosal layer can be easily separated from the mucosa, myotomy of the longitudinal and circular musculature is performed up to 6-7 cm proximally to the esophagogastric junction and completed distally by 1.5-2 cm onto the fundus. We prefer the 180 degrees anterior semifundoplication according to Dor as antirefluxplasty, which is sutured in a two-rowed manner into the two sites of the myotomy. The pitfalls are incomplete myotomy, especially at its distal, fundic site, with consecutive persistence or recurrence of symptoms, as well as occult mucosal perforations, which can be detected by intraoperative endoscopy.

Analysis of parathyroid graft rejection suggests alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages.

BACKGROUND During acute rejection of organ or tissue allografts T cells and macrophages are dominant infiltrating cells. CD4-positive T cells are important for the induction of allograft rejection and macrophages are important effector cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible NO-synthase (iNOS). In the present study we analysed whether the destruction of primarily nonvascularised parathyroid allografts is also mediated by iNOS-positive macrophages. METHODS Hypocalcaemic Lewis rats received parathyroid isografts (from Lewis donors) and allografts (from Wistar Furth donors), respectively, under the kidney capsule. Levels of serum calcium above 2 mmol/L correlated with normal parathyroid function and below 2 mmol/L with parathyroid rejection. Accelerated parathyroid allograft rejection was induced by immunisation of Lewis recipients with the allogeneic peptide P1. RESULTS Determination of serum calcium levels is a useful parameter to control parathyroid graft function, and therefore to determine allograft rejection. Macrophages positive for both major histocompatibility complex (MHC) class II molecules and costimulatory molecules accumulated in iso- and allografts, but iNOS-positive macrophages were only detectable in allografts in the presence of activated CD4-positive T cells. These results confirm a cooperation between activated T cells and intragraft macrophages to induce macrophage iNOS expression. Recipients immunised with the allogeneic peptide P1 demonstrated accelerated rejection of allografts (mean+/-SD: 9.2+/-0.9 days) in contrast to nonimmunised animals (mean+/-SD: 15.8+/-1.8 days). Allografts of P1-immunised animals were infiltrated faster by activated CD4-positve T cells and, in addition, the infiltrates of iNOS-positive macrophages were stronger than those in allografts of nonimmunised animals. CONCLUSIONS Intragraft iNOS-positive macrophages seem to be able to produce cytotoxic NO involved in the killing of allogeneic cells during the alloimmune response against primarily nonvascularised parathyroid organ grafts. Infiltrates of iNOS-negative macrophages found in parathyroid isografts were caused by antigen-independent inflammation triggered by surgically induced injury. The absence of activated T cells in isografts and their presence in allografts underlines their importance in inducing macrophage iNOS expression.

Unexpected liver failure after right hemihepatectomy for colorectal liver metastasis due to chemotherapy-associated steato-hepatitis: time for routine preoperative liver biopsy?

Dear Editor: The introduction of modern chemotherapy regimens, such as oxaliplatin and irinotecan, has led to significant improvements in the survival of patients with colorectal liver metastases. However, this new generation of agents is associated with adverse events, such as chemotherapyassociated steato-hepatitis (CASH). Until now, only sporadic reports of CASH could be found in the literature. We would like to describe the case of a 55-year old man who underwent a left hemicolectomy for nodal negative colonic adenocarcinoma. Five years after the initial operation, the patient developed a solitary liver metastasis in segments I/VII of the liver. He received 10 cycles of chemotherapy with 5-FU, folinic acid, and irinotecan over a period of 6 months, followed by bevacizumab. After a 3-month interval, he presented to undergo surgical resection. The solitary tumor involved segments I/VII and infiltrated both the right portal and the right hepatic veins. Preoperative evaluation calculated a remnant volume of 720 ml for the left hemiliver, presumably enough for a person of his weight (90 kg). Our patient underwent a right hemi-hepatectomy with resection of segment I and of the right portal vein. He received six units of packed red cells and underwent a Pringle maneuver for 37 min. The postoperative course was remarkable for liver insufficiency, characterized by III°–IV° encephalopathy and peak bilirubin levels of 8 mg/dl. Prothrombin time remained within the normal rage. Moderate doses of vasopressors were required to maintain hemodynamic stability. Creatinine values remained below 2 mg/dl. The encephalopathy and hyperbilirubinemia improved with six sessions of plasmapharesis. The patient was able to leave the intensive care unit on postop day 32 and was discharged on day 52. Microscopic pathology revealed 60% macrovesicular steatosis. The presence of vascular and steatotic changes in patients treated with chemotherapy can be a source of morbidity and mortality at the time of resection of liver metastases. In our case, although the remnant liver volume (720 ml) after the hemi-hepatectomy was theoretically adequate (body mass index of 26), and the postoperative synthetic function of the liver remained within normal range, the patient developed a severe encephalopathy that only resolved with plasmapheresis. We hope that our report will serve as a reminder of the risk of CASH and as a guide to the consideration of routine preoperative liver biopsies. Int J Colorectal Dis (2009) 24:241 DOI 10.1007/s00384-008-0570-5

Technical aspects of laparoscopic Heller myotomy for achalasia

Minimally invasive surgery has influenced the treatment of achalasia more than that of any other gastrointestinal disorder. Laparoscopic Heller myotomy has thus evolved to the first-line therapy in patients with achalasia and led to a significant change in the treatment algorithm of this disorder. The aim of this article is to present technical aspects and pitfalls of Heller myotomy with combined antirefluxplasty. After injection of 0.9% NaCl into the muscularis and submucosa of the distal esophagus and proximal fundus, whereby the submucosal layer can be easily separated from the mucosa, myotomy of the longitudinal and circular musculature is performed up to 6-7 cm proximally to the esophagogastric junction and completed distally by 1.5-2 cm onto the fundus. We prefer the 180 degrees anterior semifundoplication according to Dor as antirefluxplasty, which is sutured in a two-rowed manner into the two sites of the myotomy. The pitfalls are incomplete myotomy, especially at its distal, fundic site, with consecutive persistence or recurrence of symptoms, as well as occult mucosal perforations, which can be detected by intraoperative endoscopy.

Cranial mesohepatectomy: a challenging parenchyma-preserving operation for colorectal liver metastases

Dear Editor: The treatment of colorectal liver metastases has evolved over time. Improvements in chemotherapeutic regimens coupled with a multidisciplinary approach have resulted in a greater number of patients undergoing liver resections and major surgical challenges. Chemotherapeutic injury to the liver mandates preservation of as much parenchymal volume as possible in order to minimize the risk of liver failure. Furthermore, the potential for second and third resections for recurrent disease mandates the maintenance as much as possible of the intrahepatic anatomical relationships. Our present report describes a cranial mesohepatectomy in a case considered to be inoperable by others. A 57-year-old woman presented to our institution with a colorectal liver metastasis. Approximately 1 year ago, she had undergone a low anterior resection for a nodal negative rectal adenocarcinoma (pT3N0V0L0R0G2). Adjuvant radiochemotherapy according to the MAYO protocol had been initiated but side effects led to its discontinuation after the first cycle. A computed tomography (CT) scan at the time of presentation showed a 19 cm in diameter central solitary liver lesion infiltrating the right and middle hepatic veins. A right trisectionectomy (resection of segments 4– 8) was considered but not pursued due to the high risk of postoperative liver insufficiency (calculated remnant liver volume of 215 ml). Careful study of CT images showed a right inferior hepatic vein draining part of the lateral sector of the right liver lobe. Virtual postresection reconstruction with computer-assisted three-dimensional CT showed adequate drainage of segments 5 and 6 and partial drainage of segment 4b (379 ml) via the right inferior hepatic vein. A cranial mesohepatectomy (segments 4a, 7, and 8) was undertaken. The lesion was resected en bloc with the right and middle hepatic veins. Pathological examination of the specimen showed tumor-free margins (R0 resection). The patient tolerated the operation well, with no signs of liver insufficiency. She was discharged on postoperative day 10. Surgical resection of colorectal liver metastases requires precise anatomical study of the individual intrahepatic anatomy. Recent developments in computer-assisted imaging provide improved visualization of the hepatic vascular and segmental anatomy and allow for volumetric calculation. Image-based computer assistance and three-dimensional reconstruction are particularly useful for planning challenging liver resections, such as cranial mesohepatectomy, minimizing the risk of postoperative liver failure. Int J Colorectal Dis (2009) 24:243 DOI 10.1007/s00384-008-0610-1

Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters

BACKGROUND/AIMS This study was initiated in order to define the (co-)expression patterns of target receptor tyrosine kinases (RTKs) in human gastric adenocarcinoma and to correlate them with clinicopathological parameters. METHODOLOGY The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 was analyzed in 56 samples of human gastric adenocarcinoma and correlated with staging and survival. RESULTS VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 were expressed at relevant levels in 79%, 50%, 50%, 63%, 55% and 30%, respectively. VEGFR2, VEGFR3, and PDGFRbeta were significantly co-expressed. Thirty-four percent of gastric adenocarcinoma samples revealed a co-expression of 6 receptors, 27% expressed 5 receptors and only 23% showed expression of 3 receptors or less. Expression of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 in gastric adenocarcinoma did not significantly correlate with a higher pT-category, the presence of lymph node metastasis (pN+) or overall survival. However, a trend towards a higher pT-category was seen for expression of VEGFR1 without reaching statistical significance. CONCLUSIONS The data obtained reveal that specific RTKs are significantly co-expressed. However, co-expression of RTKs did not impact on staging or survival. It has to be further analyzed, if the expression of the respective ligands is of higher relevance than the expression of the receptor itself.

Liver resection for concomitant colorectal liver metastases and intrahepatic cholangiocarcinoma: a rare combination

The occurence of simultaneous unrelated tumors has always been of clinical interest. Although the finding of two benign primary liver lesions or of a benign and a malignant one is not infrequent, the co-existence of two unrelated malignant liver tumors is extremely rare. We herein report the case of colorectal liver metastases in association with an intrahepatic cholangiocarcinoma. A 62-year-old Caucasian female underwent resection of a ypT3 ypN0(0/30) cM0 rectal cancer after receiving neoadjuvant radiochemotherapy. Almost 6 years later, in the setting of tumor markers within normal laboratory range (carcinoembryonic antigen, <5 ng/ml, Ca 19-9, < 37U/ml), a routine follow-up computed tomography (CT) evaluation showed three new liver masses located in segments 2 and 3. The patient was subjected to a non-typical liver resection of the lesions in segments 2 and 3. Pathological exam of the 1.4and 4.6-cm lesions resected from segments 2 and 3 revealed metastatic rectal adenocarcinoma. Immunohistochemichal staining positive for cytokeratin (CK) 20 and CDX2 and negative for CK7 confirmed the diagnosis. The third lesion, 1.9 cm in size, was found to be a well-differentiated pT1 G1 pR0 cholangiocarcinoma, negative for CK20 and CDX2 and positive for CK7. Follow-up CT scan of the abdomen 5 months later detected a 0.8-cm cystic mass in segment 7 with no evidence of extra-hepatic disease. An explorative laparotomy was undertaken followed by an atypical resection of segment 7. Immunohistochemichal staining of the resected lesion, positive for CK20 and negative for CK7, was consistent with metastatic rectal adenocarcinoma. Resection margins were free of tumor. The patient is currently tumor-free, alive, and well 12 months after the third resection and 76 months after the initial operation. Tumor markers remain within normal laboratory range. To the best of our knowledge, this is the first report of a liver resection for concomitant colorectal liver metastases and intrahepatic cholangiocarcinoma. In the literature, there are only sporadic reports about colorectal metastases with intrabiliary growth, presenting as cholangiocarcinomas of the large ducts, which can be particularly difficult to distinguish morphologically from some cholangiocarcinomas. A combined immunohistochemistry of CK7 and CK20 is useful for this differentiation. In the present case, the different malignant origin of the liver lesions could be well documented in the immunohistochemistry, and a metastatic carcinoma with intrahepatic tumor growth could be excluded in this report, underlying its rarity.

Technische Aspekte der laparoskopischen Heller-Myotomie bei der Achalasie@@@Technical aspects of laparoscopic Heller myotomy for achalasia

Minimally invasive surgery has influenced the treatment of achalasia more than that of any other gastrointestinal disorder. Laparoscopic Heller myotomy has thus evolved to the first-line therapy in patients with achalasia and led to a significant change in the treatment algorithm of this disorder. The aim of this article is to present technical aspects and pitfalls of Heller myotomy with combined antirefluxplasty. After injection of 0.9% NaCl into the muscularis and submucosa of the distal esophagus and proximal fundus, whereby the submucosal layer can be easily separated from the mucosa, myotomy of the longitudinal and circular musculature is performed up to 6-7 cm proximally to the esophagogastric junction and completed distally by 1.5-2 cm onto the fundus. We prefer the 180 degrees anterior semifundoplication according to Dor as antirefluxplasty, which is sutured in a two-rowed manner into the two sites of the myotomy. The pitfalls are incomplete myotomy, especially at its distal, fundic site, with consecutive persistence or recurrence of symptoms, as well as occult mucosal perforations, which can be detected by intraoperative endoscopy.