Prognostic significance of tumor budding, desmoplastic reaction, and lymphocytic infiltration in patients with gastric adenocarcinoma.

BACKGROUND: Recent studies have shown that the tumor microenvironment significantly influences the behavior of solid tumors. In this context, Accumulated data suggests that pathological evaluation of tumor budding (TB), desmoplastic reaction (DR), and tumor-infiltrating lymphocytes (TILs) may be crucial in determining tumor behavior in the gastrointestinal tract. Regarding gastric adenocarcinoma (GAC), although some results suggest that TB and TILs may be effective in determining the course of the disease, the data do not agree. Moreover, very few studies have investigated the relationship between DR and survival. At present, the associations between tumor TB, DR and TILs in GAC patients have not been determined. AIM: To establish the relationships between TB, DR, and TILs in patients with GAC and to assess their influence on prognosis. METHODS: Our study group comprised 130 patients diagnosed with GAC. The definition of TB was established based on the International TB Consensus Conference. The DR was categorized into three groups according to the level of tumor stroma maturation. The assessment of TILs was conducted using a semiquantitative approach, employing a cutoff value of 5%. The statistical analysis of the whole group and 100 patients with an intestinal subtype of GAC was performed using SPSS version 27. RESULTS: A significant correlation between peritumoral budding (PTB) and intratumoral budding (ITB) was noted (r = 0.943). Tumors with high PTBs and ITBs had a greater incidence of immature DRs and low TILs (P < 0.01). PTB and ITB were associated with histological subtype, lymph node metastasis (LNM), and stage (P < 0.01). ITB, PTB, LNM, DR, and stage were significant risk factors associated with poor prognosis. The multivariate Cox regression analysis identified ITB, PTB, and LNM as independent prognostic variables (P < 0.05). In intestinal-type adenocarcinomas, a positive correlation between PTB and ITB was noted (r = 0.972). While univariate analysis revealed that LNM, stage, PTB, ITB, and DR were strong parameters for predicting survival (P < 0.05), only PTB and ITB were found to be independent prognostic factors (P < 0.001). CONCLUSION: TB may be a potential prognostic marker in GAC. However, further studies are needed to delineate its role in pathology reporting protocols and the predictive effects of DR and TILs.

Clinicopathologic Evaluation of CD80, CD86, and PD-L1 Expressions with Immunohistochemical Methods in Malignant Melanoma Patients.

OBJECTIVE: Diagnostic and prognostic biomarkers for malignant melanoma are crucial for treatment and for developing targeted therapies. Malignant melanoma is a highly immunogenic tumor, and its regression, treatment, and prognostic evaluation are directly related to escape from immune destruction. Therefore, we aimed to determine the expression levels of CD80, CD86, and PD -L1 in malignant melanoma tissue samples by immunohistochemistry and to investigate the possible relationship between these proteins and the clinicopathological features in this study. MATERIAL AND METHODS: Hematoxylin and eosin staining and immunohistochemical staining for CD80, CD86, and PD-L1 were evaluated for clinical data, survival, prognosis, tumor location, malignant melanoma subtypes, tumor size, and prognostic findings. RESULTS: Higher survival rates were observed in patients with lower PD-L1 staining scores in the tumor. The 5-year survival was higher in patients with CD80-positive and CD86-positive biopsies. Mortality was lower in superficial spreading melanoma and Lentigo maligna melanoma types, whereas staining positivity of CD80 and CD86 was higher. Furthermore, a relationship between clinical stage and Breslow thickness ( < 2mm/≥2mm), tumor ulceration, lymph node metastasis, and CD80 and CD86 expression was also identified. CONCLUSION: Our findings suggest that PD-L1, CD80, and CD86 expression are essential in malignant melanoma and could be used as prognostic markers.

Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Tumor budding as a potential prognostic marker in determining the behavior of primary liver cancers.

Hepatocellular (HCC) and intrahepatic cholangiocarcinoma (ICC), the most common primary tumors of the liver, are among the most important causes of cancer deaths worldwide. Because patients with primary liver tumors are frequently diagnosed at an advanced stage and have high mortality, many efforts have been made to identify new markers to determine their behavior and treatment, similar to those in other solid organ tumors. Recently, morphological assessment of tumor budding (TB) has been revealed as a promising prognostic finding to predict tumor behavior and survival across several different tumor types. Currently, the TB score in colorectal cancer has been revealed as an important parameter in pathology report protocols to determine the course of the disease. Regarding the liver, despite enormous data showing that many mechanisms involved in TB are associated with tumor behavior in both HCC and ICC, studies focusing on the role of TB in predicting the behavior and prognosis of these tumors have started to be investigated very recently. The purpose of this review is to present data about TB in primary tumors of the liver, pointing out the potential role of this parameter in determining the course of the disease, and emphasize the need to increase the number of further studies focusing on the evaluation of this parameter with an overview of the mechanisms involved in TB.

CTCFL expression is associated with cerebral vascular abnormalities.

CTCFL is expressed in testis, oocytes and embryonic stem cells, and is aberrantly expressed in malignant cells, and is classified as a cancer-testis gene. We have previously shown by using a tetracycline-inducible Ctcfl transgene that inappropriate expression of Ctcfl negatively impacts fetal development and causes early postnatal lethality in the mouse. The affected pups displayed severe vascular abnormalities and localized hemorrhages in the brain evocative of cerebral cavernous malformations (CCM) and arteriovenous malformations (AVM) in humans. Thus, we aim to analyze; a) the presence of CCM-related proteins CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10 in Ctcfl transgenic animals and, b) whether there is CTCFL expression in human CCM and AVM tissues. Ctcfl transgenic animals exhibited increased CD31 expression in vascular areas of the dermis and periadnexal regions but no difference was observed for vWF and α-SMA expressions. CCM-related proteins CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10 were aberrantly expressed in coronal sections of the head in transgenic animals. We also observed CTCFL expression in human CCMs and AVMs. The induced expression of CTCFL resulting in vascular brain malformations in mice combined with the presence of CTCFL in human vascular malformations provide new insights into the role of this gene in vascular development in humans.

The role of insulin-like growth factor in Acrochordon Etiopathology.

BACKGROUND: There are reports that acrochordon (skin tag), the most common fibroepithelial tumor of the skin, may be associated with metabolic syndrome components, particularly insulin metabolism disorders. However, to the best of our knowledge, there is no study examining its association with insulin resistance and tissue levels of insulin-like growth factor 1 receptor (IGF-1R) and insulin-like growth factor 2 receptor (IGF-2R). METHODS: Thirty patients with at least one acrochordon in their body who had no known history of diabetes mellitus and a control group comprised 30 individuals who had no acrochordon or no known history of diabetes mellitus were included. The tissue expression of IGF-1R and IGF-2R were investigated via immunohistochemical assessment in both groups. RESULTS: In the group with acrochordon, IGF-1R and IGF-2R expression was found to be significantly higher compared to the control group (p < 0,01). Using logistic regression analysis, an increase in serum insulin, serum IGF-1 and HOMA-IR levels was found to be associated with the expression levels of IGF-1R and IGF-2R. CONCLUSION: These findings support the view that insulin metabolism disorders should be evaluated in patients with acrochordon. Our study indicates that IGF receptors may have an effect on acrochordon pathogenesis and that acrochordon etiology and related conditions can be clarified by detection of parameters that influence receptor levels.

Incidental Collision Tumor of Hepatocellular Carcinoma and Neuroendocrine Carcinoma.

The composite tumors of the liver are very rare, including the coexistence of HCC (hepatocellular carcinoma) with NEC (neuroendocrine carcinoma). The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics, behaviors and treatments. Herein is described an incidental collision tumor of HCC-NEC, along with a review of the literature focusing on their clinicopathological findings and prognosis. The tumor presented here was found incidentally in the hepatectomy specimen of a 56-year-old man who had undergone liver transplantation for rapidly progressive liver failure because of alcoholic hepatitis and cirrhosis. Imaging and laboratory examinations did not demonstrate tumor-related findings. During macroscopic examination, two sharply defined and distinctive areas (1.7 cm and 0.6 cm dimension respectively) were detected among the cirrhotic nodules. The characteristic histopathological features and immunohistochemical findings allowed a diagnosis of HCC-NEC to be made. There was no evidence of recurrence and metastasis after 10 months following surgery. The present case and review revealed that these tumors are frequently found in older ages and males. Although serum markers are valuable in the discrimination of malignant tumors, their absence cannot completely rule out composite HCC-NEC. Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry. The NEC component might influence the treatment strategy and eventually the outcome of the patient. In conclusion, the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors, especially in patients with the chronic liver disease.

Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was Refractory to Corticosteroid and Omalizumab Treatments.

Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP). Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP. Here we present a young BP patient who responded well to rituximab therapy and was refractory to conventional and omalizumab therapies although he had elevated IgE levels and eosinophilia. Our case supports the knowledge about the effectiveness and safety of rituximab not only in pemphigus but also in BP. On the other hand, although it did not work in our case, omalizumab may be a potentially effective agent in some carefully selected patients with certain subtypes of BP.

A new lateral thoracic artery perforator flap design with multiple vascular territories in rats.

BACKGROUND: To describe a new design for an extended lateral thoracic artery (LTA) perforator flap and investigate its anatomical, dynamic, and potential territories. MATERIALS AND METHODS: To assess vascular territories, rats were randomized according to LTA perforator flap type into the surgical groups A, hemidorsal island flap; B, entire dorsal island flap; and C, reduced-size dorsal island flap. RESULTS: On postsurgical day 7, the surviving flap areas were 95%, 92%, and 89% in groups A, B, and C, respectively. Necrosis most commonly occurred in the contralateral LTA territories in groups B and C. The immunoreactivities of intercellular adhesion molecule 1 and vascular endothelial growth factor receptor 2 in dynamic territories, as choke vessel markers, were increased. CONCLUSIONS: We clarified the LTA perforator flap nomenclature and defined its pedicle course and anastomosing patterns; furthermore, we demonstrated that the LTA perforator did not anastomose with its counterpart because of its unidirectional, oblique, and craniocaudal course. The LTA perforator flap was found to be a good model comprising multiple vascular territories and exhibiting continuous necrosis.

A Case of Disseminated Hypopigmented Keratoses Improved with Oral Acitretin.

Disseminated hypopigmented keratosis is a distinct clinical entity and only few cases have been reported so far. Here, we present a 21-year-old man with almost 10-year history of hypopigmented, nonfollicular, keratotic lichenoid papules occurring on the extensor surfaces of the extremities, back and lumber region. Histopathological examination showed orthohyperkeratosis, irregular acanthosis, and sporadic papillomatosis with a normal amount of melanin and number of melanocytes. In addition, no marked inflammation or melanophages were seen. In order to exclude other possible causes, we performed laboratory tests and radiological examination which were all found to be normal. As the clinical and histopathological features of our patient were taken into account, it was considered to be compatible with the diagnosis of disseminated hypopigmented keratoses. So far, only topical therapies have been used with failure in the previously reported cases except one patient. Considering the extensive lesions, we treated the present patient with 5% salicylic acid in addition to oral acitretin and significant regression in all lesions was achieved, particularly on the keratosis.

Circumflex scapular artery myocutaneous and/or vascularized scapular chimeric flap.

BACKGROUND: Chimeric osteomyocutaneous flaps harvested from the subscapular artery system have been used in clinical practice. We describe the use of a novel circumflex scapular artery myocutaneous and/or vascularized scapular chimeric flap in a rat model and demonstrate optimal skin flap dimensions. MATERIALS AND METHODS: An 8 × 4-cm-rectangular skin flap based on the circumflex scapular artery flap was harvested, and the mean percentage of the surviving flap area and the necrotic area were calculated to be 71% ± 17.9% and 29% ± 17.9%, respectively. Using flap dimensions determined in the first part of our study, a 4 × 3-cm quadrangular portion of skin was marked over the scapula, and the serratus anterior muscle and a portion of the scapular bone were included in our chimeric flap model. RESULTS: The mean percentages of the surviving flap and necrotic areas were 74% ± 6% and 25% ± 6%, respectively. Microangiographic and histologic studies revealed the vascularity of the skin island and identified the branches of the circumflex scapular artery that supplied the bone and muscle. CONCLUSIONS: The circumflex scapular artery myocutaneous and/or vascularized partial scapular chimeric flap may be considered a branch-based chimeric flap and can be an acceptable flap model due to its simplicity, reliability, and consistent vascularity. Furthermore, this flap may have potential applications in studying chimeric flap hemodynamics.

The Effect of Normovolemic and Hypervolemic Hemodilution on a Perforator Flap with Twisted Pedicle Model: Experimental Study in Rats.

BACKGROUND: Several studies showed the detrimental effect of pedicle torsion on flap survival; however, the impact of hemodilution in this peculiar condition has never been investigated. This study evaluated the effect of acute normovolemic and hypervolemic hemodilution on flap survival in a perforator flap with twisted pedicle model. METHODS: Sixty-three female Wistar rats were divided into three groups of 21 rats each: group 1, superficial inferior epigastric artery flap, which was elevated bilaterally and transposed back to the abdominal wall with different angles of rotation (i.e., 90, 180, 270, and 360 degrees); group 2, surgery with previous acute normovolemic hemodilution; and group 3, surgery with previous acute hypovolemic hemodilution. Normovolemic hemodilution was obtained, simultaneously removing 2 cc of blood and replacing it with an equal volume of isotonic sodium chloride 0.9% (two-thirds) plus hydroxyethyl starch 6% (one-third). Hypervolemic hemodilution was obtained by hemodilution and a 20 percent blood volume expansion. Microangiography of the flap and histopathologic analyses were performed. RESULTS: Mean hematocrit values after hemodilution were 27.80 ± 0.04 percent for the acute normovolemic hemodilution group and 27.01 ± 0.03 percent for the acute hypovolemic hemodilution group. Twisting the pedicle at 90, 180, and 270 degrees had no effect on flap survival in all groups. However, 360-degree pedicle torsion showed flap edema, congestion, and necrosis. CONCLUSIONS: The authors' hemodilution protocol is an effective and reliable method that could be used to further investigate the impact of the hemodynamic changes that occur during hemodilution on flap microcirculation. The results obtained sustain the existence of a strong correlation between necrosis rate and hemodilution.

Late relapse of testicular cancer: Recurrence after 24 years and treatment with chemotherapy alone.

Late relapse of testicular cancer, defined as >2 years interval between initial treatment and recurrence, is a rare disease with the incidence rate of 2.6%. Due to its chemoresistant features, treatment options of late relapses are controversial while surgical approach and cisplatin-based chemotherapies can be considered. We report here a patient with nonseminomatous germ cell tumor who experienced relapse 24 years after his first diagnosis. After detecting left supraclavicular lymphadenopathy and absence of any other malignant lesion in positron emission tomography-computerized tomography, patient was treated with three cycles of VeIP regimen (vinblastine/ifosfamide/cisplatin). Second complete response to this treatment was achieved with chemotherapy alone.

The Effect of Normovolemic and Hypervolemic Hemodilution on a Microsurgical Model: Experimental Study in Rats.

BACKGROUND: Nowadays, postoperative flap perfusion impairment still occurs in free flap surgery; despite several studies on microcirculatory physiology, the effect of hemodilution is still extremely controversial. The aim of this study was to investigate the impact of acute normovolemic and hypervolemic hemodilution on the incidence of flap survival rate in a microsurgical rat model. METHODS: Forty female Wistar rats were divided into four groups of 10 rats each: in group 1, a superficial inferior epigastric artery flap was elevated until femoral vessels were isolated, sectioned, and anastomosed without hemodilution; in group 2, surgery with previous acute normovolemic hemodilution was performed; in group 3, surgery with previous hypervolemic hemodilution was performed; and group 4, was used as a negative control to validate the microsurgical model. Normovolemic hemodilution was obtained, with simultaneous removal of an average of 2.25 cc of blood and replacement with an equal volume of isotonic sodium chloride 0.9 percent and hydroxyethyl starch 6 percent. Hypervolemic hemodilution was obtained by hemodilution and a 20 percent blood volume expansion. Microangiography of the flap and histopathologic analyses were performed. RESULTS: Mean hematocrit values after the hemodilution were 26.80 ± 0.05 percent for group 2 and 28.11 ± 0.04 percent for group 3. Skin flap survival and vascularization after 7 days were significantly higher in both hemodiluted groups compared with the control group (p < 0.05). CONCLUSION: Hemodilution was an effective way of providing better microcirculatory blood perfusion, increasing significantly the flap survival rate in the authors' microsurgical model.

Clinicopathological evaluation of cutaneous leishmaniasis in the mediterranean region of Turkey.

OBJECTIVE: Cutaneus leishmaniasis, a chronic self-limited disease of the skin, is usually caused by Leishmania Tropica. It is endemic in Southeastern Anatolia. The definitive diagnosis depends on demonstration of the parasites by smear and culture or its identification in tissue section. This study aimed to evaluate clinical and histopathological skin lesions in cutaneous leishmaniasis cases in Antalya, Turkey. MATERIAL AND METHOD: Our study included 28 patients diagnosed with cutaneous leishmaniasis at the Pathology Department of Akdeniz University Medical Faculty. Histopathological sections were stained with Haematoxylin-Eosin, Giemsa or Leishman for visual examination of cellular components by two dermatopathologists. The epidermal (acanthosis, hyper-parakeratosis, atrophy, lymphocytic exocytosis) and dermal changes that may indicate lymphohistiocytic infiltration and granuloma formation were investigated. The parasitic load was classified according to the modified Ridley's parasitic index. RESULTS: Out of 28 cases, 11 had hyperparakeratosis, 17 had orthokeratosis, 20 had acanthosis, 4 had epidermal atrophy, and 7 had exocytosis. Typical epithelioid cell granulomas with giant cells and a rim of lymphocytes were present in 16 cases. Leishman-Donovan bodies were extremely rare in typical granulomatous lesions. The other 12 cases showed lymphohistiositic infiltration, giant cells and prominent plasma cells. There were numerous Leishman-Donovan bodies in these lesions. CONCLUSION: We investigated the epidermal and dermal changes that would facilitate the histopathological diagnosis of cutaneous leishmaniasis in this study. We found that atrophy, acanthosis, and orthokeratosis were early stage indicators, while exocytosis, hyperparakeratosis, and atrophy were indicative of late stage disease.

Cytomegalovirus colitis with common variable immunodeficiency and Crohn's disease.

Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID) three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn's disease (CD) due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and he died in the postoperative seventh day. Laboratory analysis was seronegative. CMV inclusion containing cells were detected in postmortem biopsies taken from liver, lungs, and lymph nodes.