Bogumiła Ciseł

Circulating microenvironment of CLL: are nurse-like cells related to tumor-associated macrophages?

B-cell chronic lymphocytic leukemia (B-CLL) is one of the most common hematologic malignancies in Western countries. Accumulation of leukemic lymphocytes in peripheral blood, bone marrow and secondary lymphatic organs of CLL patients is due to decreased apoptosis rather than to increased proliferation. The former is driven by signals from a specific microenvironment, created by stromal cells of mesenchymal origin, follicular dendritic cells, T lymphocytes and others. Nurse-like cells (NLCs) were first described to differentiate from peripheral blood mononuclear cells of CLL patients in vitro, then they have been also found in proliferation centers of their lymphatic tissues. Like tumor-associated macrophages (TAMs) in solid tumors, nurse-like cells promote survival of CLL lymphocytes. NLC gene expression patterns suggest their similarity to TAMs and differ between patients depending on ZAP70 protein expression status. NLC number in vitro corresponds with CD14 expressing cell count and beta-2-microglobulin serum level, and positively correlates with leukemic lymphocyte viability. As NLCs strongly express genes for adhesion molecules and secrete chemokines of antiapoptotic activity, they should be considered as a target for anti-microenvironment therapy of this incurable disease.

Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology

In Western countries the majority of gastric cancers (GC) are usually diagnosed in advanced stages reporting a 5-year survival rate of only 26%. The Laurén classification of GC was most widely used in clinical practice since it reflects GC morphology, epidemiology, tumor biology, clinical management and outcome. Despite the initial promise of individualizing antitumor treatment, the management of GC still remains relatively broad and general. Apart from clinical staging, molecular profiling enables targeting of the identified underlying alterations, rather than histology. In contrast to breast carcinoma, molecular classification of GC does not yet imply treatment modality. Molecular classifications of GC and their therapeutic implications are therefore extensively studied. The current proposed molecular divisions of GC come from three different parts of the world where different standard treatment modalities for advanced GC are recommended. Wider use of GC molecular subtyping may solve problems, such as susceptibility to novel systemic therapy regimens or selection of patients for aggressive surgery and targeted adjuvant/conversion therapy. In any case, the rapid entry of novel molecular targeted therapies into routine oncology practice clearly underscores the urgent need for clinicians to be aware of these new possibilities.

Duodenal obstruction due to annular pancreas associated with carcinoma of the duodenum

Annular pancreas, the second most common anomaly of the pancreas, is the development of a ring of pancreatic tissue that surrounds and often embraces the duodenum. It was first described by Tiedelmann in 1818 and named “annular pancreas” by Ecker in 1862 [1]. It is usually present in childhood, with symptoms due to duodenal obstruction. In 50% of cases, clinical manifestations become visible after childhood, with abdominal pain, chronic duodenal obstruction, peptic ulceration, obstructive jaundice, pancreatitis, and pancreatic head mass [2, 3]. Therefore, duodeno-jejunostomy is usually applied to relieve strictures caused by such an annulus. Bypass surgery is the treatment of choice [4]. Primary duodenal carcinoma is rare and represents 0.3% of all gastrointestinal malignancies and 25–35% of malignant tumours of the small intestine [5, 6]. Resectability and the presence of distant metastatic disease are the strongest determinants of outcome for patients with duodenal adenocarcinoma. In cases of cancers of the first and second part of the duodenum, the most common procedure is pancreaticoduodenectomy. Despite advancements in techniques of diagnosis and resection and decreased perioperative mortality and morbidity, 5-year survival varies from 37% [7] to 57% [8]. Malignancy in the setting of annular pancreas is an unusual event, and hence only a few cases associated with pancreatic carcinoma, ampullary carcinoma, and cholangiocarcinoma have been reported [9–13]. Only 1 case of annular pancreas associated with duodenal carcinoma has been reported, but without description of the follow-up [14]. We report a case of duodenal carcinoma in a patient with an annular pancreas treated with radical surgery with complete follow-up data. A 53-year-old lady suffered from nausea, post-prandial fullness, and vomiting, and weight loss. She was diagnosed (endoscopy Figure 1, CT scan of the abdomen Figure 2) to have duodenal obstruction with gastric bezoar. The upper intestinal contrast study findings of annular filling defect in the duodenum, prestenotic dilatation, and reverse peristalsis in the proximal segment were suggestive of annular pancreas. A pathology report of the endoscopic biopsy material taken from the stenotic part of the duodenum revealed suspicion of malignancy, i.e. atypic cells. The patient was scheduled for a laparotomy with intraoperative pathological investigation of the suspected lesion, and if malignancy is proven a pancreaticoduodenectomy is anticipated. During the operation a band of fibrous (probably pancreatic) tissue of hard texture encircling the second part of the duodenum was found (Figure 3). Division of the pancreatic ring was done and the abnormal tissue sent for immediate pathology. Once malignant diagnosis was confirmed, and classical Kausch-Whiple pancreaticoduodenectomy with standard lymphadenectomy was done without perioperative complications. The resection specimen had been routinely fixed in buffered 10% formaldehyde and embedded in paraffin wax (Figure 4). Operative time was 300 min, and blood loss was 420 ml. The postoperative course was uneventful; therefore, the patient was discharged from the hospital on the sixteenth postoperative day. A definitive pathological report confirmed tubular carcinoma (G2) of the duodenum associated with the annular pancreas with no lymph node involvement (pT2N0M0) (Figures 5–8). No adjuvant chemotherapy was administered. The patient was followed-up every 3 months thereafter for the first 3 years. In the first (2008) and second year (2009) of the follow-up, abdominal CT-scan was done without signs of recurrence. After 54 months the patient became heavily jaundiced and cachectic, and was therefore hospitalised. Advanced loco-regional recurrence was found on MR cholangiogram, with no liver metastases. The patient died, and no autopsy was performed. Figure 1 Endoscopic view of the duodenum showing ulceration with duodenal stenosis at the second portion Figure 2 Computed tomography scan image revealing a significant dilatation of the stomach with bezoar and the proximal duodenum Figure 3 Intraoperative view of the annular pancreas encircling the second part of the duodenum Figure 4 Cross-sectional view showing the duodenum surrounded by the pancreas tissue (annular pancreas) Figure 5 Tubular adenocarcinoma of the duodenum. Neoplastic tubules border on normal duodenal glands (four-micron sections of representative blocs of the lesion were stained with haematoxylin and eosin (H + E); 100×) Figure 8 Fragment of the pancreas (annular pancreas), which is not involved in cancerous infiltrate (H + E; 100×) Figure 6 Tubular adenocarcinoma of the duodenum. Neoplastic tubules border on normal duodenal glands (four-micron sections of representative blocs of the lesion were stained with haematoxylin and eosin (H + E); 200×) Figure 7 Neoplastic infiltrate of the muscular coat of the duodenum encompasses both an inner circular layer and an outer longitudinal layer (H + E; 100×) Annular pancreas is a rare congenital abnormality, and in adult patients it presents with clinical features that differ from those seen in newborns [15]. Duodenal obstruction is a rare symptom of annular pancreas in adults. It is necessary to remember about the coexistence of the annular pancreas when patients with pancreatic or periampullary malignancies are complicated with unexpected obstruction of the second portion of the duodenum in proportion to the size [9]. Features in the adult patient include peptic ulceration, duodenal obstruction, acute pancreatitis, and obstructive jaundice. Treatment strategies for annular pancreas with obstructive jaundice remain controversial, but usually pancreaticoduodenectomy is necessary [2]. In adult patients pancreatic head malignancy usually produces jaundice, and more rarely duodenal obstruction. Nearly always the main cause of this clinical picture is pancreatic head carcinoma, but pancreas annulare should be taken into consideration. The duodenal ring should always be verified on pathological examination since it may harbour this rare type of adenocarcinoma. In adult patients with duodenal obstruction due to annular pancreas, consideration of associated or coexisting duodenal malignancy is mandatory. Only radical surgery (pancreaticoduodenectomy) may provide long-term survival in such cases.

Current challenges in gastric cancer surgery: European perspective

Gastric cancer (GC) remains one of the most common causes of cancer death worldwide with expected 5-year survival rates around 25% in Western countries. In order to improve treatment strategy, a most effective staging process should be completed. A novel TNM staging for GC has been proposed recently, along with a separate staging system for GC patients who underwent preoperative therapy (ypStage). Availability of high-quality imaging and access to diagnostic laparoscopy with lavage cytology should be applied while planning the multimodal therapy. In the European setting, GC treatment is based on a combination of surgery and perioperative chemotherapy. However, in selected groups of patients with high risk of locoregional recurrence, adjuvant chemoradiotherapy should be considered. New epidemiological trends of GC in the Western countries include an upward shift in the location of the primary tumour and a relative increase of advanced and diffuse type tumours. These trends dictate modification of surgical techniques towards a more individualized GC treatment approach.

Liver metastases from gastric carcinoma: A Case report and review of the literature

Gastric carcinoma (GC) is the fifth most common malignancy worldwide but the third leading cause of cancer death, and surgery remains the only curative treatment option. Prognosis of patients with liver metastases from gastric carcinoma (LMGC) is poor, and the optimal treatment of metastatic gastric cancer remains a matter of debate. In 2002, a 53-year-old male patient with GC and synchronous oligometastatic lesion in liver VIII segment underwent a total gastrectomy combined with metastasectomy. The pathologic diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), which was treated with adjuvant chemotherapy (cisplatin, epirubicin, leucovorin, and 5-fluorouracil). In 2012, abdominal ultrasound and percutaneous liver biopsy revealed recurrence of the metastasis in the right liver lobe. Progression of the disease was observed after palliative chemotherapy (epirubicin, oxaliplatin, and capecitabine). Nevertheless, an extended right hemihepatectomy, with excision of segments 1, 4A, 5, 6, 7, and 8, was still performed. Pathologic examination confirmed large KRAS- and HER2-negative LMGC. The patient is alive and free of disease 47 months after the repeated hepatectomy and 13 years after removal of the primary GC and synchronous liver metastasis. Based on review of 27 articles, 5-year overall survival rate following gastrectomy and liver metastasectomy may reach 60%, with median survival time up to 74 months. Although the combination of aggressive surgical approach with systemic therapy for LMGC is controversial, it may allow favorable outcome. Careful selection of patients based on evaluable predictive factors for R0 surgical resection of both primary tumor and liver metastases can lead to cure, as shown in our case presentation, where a 10-year relapse-free survival was observed, followed by successful repeated hepatectomy due to liver metastases.

Treatment of peritoneal metastases from gastric carcinoma

Abstract Patients with advanced gastric cancer and positive peritoneal cytology and/or peritoneal dissemination are deemed to be incurable and to hold dismal prognosis. So far, the only treatment option for these patients has been palliative systemic (chemo)therapy. However, for the last three decades, great progress has been made in attempts to treat (potential) peritoneal dissemination by means of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) after preoperative systemic therapy. This review is focused on the recent achievements of this multimodal strategy. Additionally, the review stands as background for the 4th International Conference “Advances in Surgical Oncology” that was held at the Medical University of Lublin (Poland) in November 2017, and dedicated to cytoreductive surgery and HIPEC for advanced gastric cancer.

Wyniki leczenia chorych na nowotwory złośliwe z przerzutami do wątroby: 8-letnie doświadczenie jednego ośrodka

Wstep. Leczenie chirurgiczne przerzutow nowotworow litych do wątroby powinno odbywac sie w ramach zespolu wielodyscyplinarnego. Cel pracy. Celem pracy jest ocena wynikow leczenia skojarzonego chorych na rozne nowotwory lite z przerzutami do wątroby przez zespol wielodyscyplinarny jednego ośrodka onkologicznego w ciągu ostatnich 8 lat. Material i metody. Retrospektywną analizą objeto 166 chorych (84 kobiety i 82 mezczyzn) w wieku od 19 do 78 lat (średnia 58 ± 11,2), leczonych z powodu przerzutow do wątroby pierwotnych nowotworow litych o roznej lokalizacji, z wyjątkiem guzow neuroendokrynnych. Kazdorazowo rozwazano okolooperacyjne leczenie systemowe zgodnie z aktualnymi zaleceniami Polskiej Unii Onkologii. Wyniki. W czasie obserwacji (mediana 35 miesiecy) zmarlo 46% chorych. Resekcje wątroby wykonano u 107 (65%)chorych, w tym u 19 chorych polączono je z (RF-)termoablacją zmian przerzutowych, ktorą wykonano jako samodzielny zabieg u dalszych 59 (36%) chorych. Śmiertelnośc pooperacyjna wyniosla 1,2%. Powiklania II° wg klasyfikacji Clavien-Dindo wystąpily u 33 (19,8%) chorych, natomiast III° i IV° — u 8 (4,8%) chorych. Przezycia 1-roczne, 3-letniei 5-letnie wyniosly odpowiednio 78%, 41% i 37%. Piecioletnie przezycia calkowite u chorych na raka jelita grubego po resekcjach przerzutow metachronicznych wyniosly 48%. Wnioski. Skojarzone leczenie chorych na nieendokrynne nowotwory lite z przerzutami do wątroby przez zespol wielodyscyplinarny jest bezpieczne i skuteczne. W starannie dobranej grupie chorych mozna osiągnąc blisko 50% calkowitych przezyc 5-letnich. Resekcja wątroby jest optymalną metodą leczenia chirurgicznego przerzutow do wątroby.

Rola białka ABI1 w nowotworach przewodu pokarmowego Przegląd literatury

Nowotwor jest schorzeniem, ktore powstaje w wyniku zalamania sie mechanizmow kontrolujących prawidlowy wzrost i roznicowanie komorki. Z procesem tworzenia przerzutow nowotworowych ściśle związane są zaburzenia polimeryzacji aktyny. Do najwazniejszych czynnikow regulatorowych polimeryzacji aktyny nalezy wieloproteinowy kompleks bialek WAVE, w sklad ktorego wchodzi miedzy innymi bialko Abl interactor1 (ABI1). Uwaza sie, ze zrozumienie roli bialka ABI1 moze w przyszlości pomoc w poznaniu mechanizmow koordynacji polimeryzacji aktyny i proliferacji komorkowej, ktore ulegają zaburzeniu w komorkach nowotworowych. Badania wykazują, ze w przebiegu chorob nowotworowych ABI1 odgrywa podwojną role: wzrost ekspresji tego bialka wplywa na rozwoj i progresje inwazyjnego raka piersi, raka jajnika, raka jelita grubego, a takze przewleklej bialaczki szpikowej i ostrej bialaczki limfoblastycznej Ph+, z drugiej strony wplywa na supresje guza w nowotworach zolądka i prostaty. Analiza wynikow badan probek tkankowych pacjentow po gastrektomii z powodu raka wykazala silną zaleznośc pomiedzy ekspresją bialka ABI1 a stopniem zroznicowania nowotworu, zaawansowaniem procesu nowotworowego oraz liczbą zajetych wezlow chlonnych. Nalezy podkreślic, ze zwiekszenie poziomu ekspresji ABI1 nie jest ograniczone tylko do procesu nowotworzenia, ale mozna je zaobserwowac takze w przypadku zmian zapalnych i innych bardzo wczesnych zmian rozrostowych, ktore niekoniecznie muszą transformowac w kierunku raka, jak na przyklad polipy hiperplastyczne. Dalsze badania ekspresji ABI1 na poziomie RNA i bialka umozliwią ocene jego wartości prognostycznej i wyjaśnią, czy moze on byc celem interwencji terapeutycznej.