In the current report by Nowicki et al. the authors review and discuss the probable role of substance P in childhood leukemias and solid bone cancers, and the use of substance P antagonists for treatment (1). As reviewed by the authors, there is much evidence to support a role for substance P in carcinogenesis. Others have suggested substance P may induce mitogenesis through activation of neurokinin-1 recep...
In the current report by Nowicki et al. the authors review and discuss the probable role of substance P in childhood leukemias and solid bone cancers, and the use of substance P antagonists for treatment (1). As reviewed by the authors, there is much evidence to support a role for substance P in carcinogenesis. Others have suggested substance P may induce mitogenesis through activation of neurokinin-1 receptor (2), and inhibition of substance P signal transduction may indeed prove to be an effective treatment option (3). In these days of molecular medicine, specific targets for the treatment of neoplasms are continuously being sought (4, 5).
References
1. Nowicki M, Ostalska-Nowicka D, Kondraciuk B, and Miskowiak B. The significance of substance P in physiological and malignant hematopoiesis. J Clin Pathol 2006, on-line, 15 December 2006.
2. Esteban F, Munoz M, Gonzalez-Moles MA, Rosso M. A role for substance P in cancer promotion and progression: a mechanism to counteract intracellular death signals following oncogene activation or DNA damage.
Cancer Metastasis Rev. 2006; 25(1):137-45
3.Yamaguchi K, Richardson MD, Bigner DD, Kwatra MM. Signal transduction through substance P receptor in human glioblastoma cells: roles for Src and PKCdelta. Cancer Chemother Pharmacol. 2005;56(6):585-93.
4. Herbst RS, Lippman SM. Molecular signatures of lung cancer- toward personalized therapy. N Engl J Med. 2007; ;356(1):76-8.
5. Muss HB. Targeted therapy for metastatic breast cancer. N Engl J Med. 2006; 355(26):2783-5.
We read with interest the article by Mescoli et al. on the high prevalence of isolated tumours cells in regional lymph nodes from pN0 colorectal cancer (CRC). [1] Based on a detailed study of resected lymph nodes, Mescoli et al reported that more than 50% of pN0-CRC patients have
isolated tumour cells (ITC) in the mesenteric lymph nodes and ITC status significantly correlated with cancer stage and vascular c...
We read with interest the article by Mescoli et al. on the high prevalence of isolated tumours cells in regional lymph nodes from pN0 colorectal cancer (CRC). [1] Based on a detailed study of resected lymph nodes, Mescoli et al reported that more than 50% of pN0-CRC patients have
isolated tumour cells (ITC) in the mesenteric lymph nodes and ITC status significantly correlated with cancer stage and vascular cancer invasion. The existence of nodal micrometastases has been previously reported in lung and breast cancers and probably occurs with all malignancies. [2,3] Izbicki et al. in a similar study on NSCLC, reported micrometastases in 27.4% of pathological N0 and 45% of pathological N1 histological negative mediastinal nodes using more sensitive monoclonal immunostaining methods.
[2] The current study further contributes to the increasing evidence that what clinicians considered as early stage cancers are probably systemic in nature by the time of diagnosis or treatment. This is important as it highlights 3 major relevant points. Firstly, with supporting studies now reporting that lymphogenesis in addition to previously known angiogenesis predicting tumour spread, it is becoming very clear how inadequate the current staging modalities are, which as yet does not take into account the presence of ITC. Secondly, all surgical tumour resection should include at least a sampling of the local regional lymph nodes in all cancers and using immunohistochemistry will provide clinicians with a more accurate system of tumour staging. The inclusion of local regional lymph nodes sampling is important and in a study by Chong et al., the inclusion of systematic mediastinal lymph nodes dissection in early clinical N0-1 NSCLC, reported the presence of pathological N2 disease in 27% of cases who were considered early NSCLC using current clinical staging methods. [4] Lastly, with the existence of ITC in local regional lymph nodes of early stage cancers, the question arises whether adjuvant chemotherapy has any beneficial role. Certainly the benefit of adjuvant chemotherapy in early stage 1B NSCLC has in recent years been proven with a reported 5%
overall survival benefit. [5] Any beneficial effects of adjuvant chemotherapy in early stage cancers will certainly have to outweigh the risk of side effects associated with current chemotherapy regimens and perhaps future development of chemotherapy regimens with better safety profile and fewer or even no side effects may yet shift this balance and improve the current survival curve of early malignancies further.
Reference
1. Mescoli C, Rugge M, Pucciarelli S, et al. High prevalence of isolated
tumour cells in regional lymph nodes from pN0 colorectal cancer. J Clin Pathol. 2006; 59:870-4. Epub 2006 Apr 7.
2. Izbicki JR, Passlick B, Hosch SB, et al. Mode of spread in the early phase of lymphatic metastasis in non-small cell lung cancer: significance of nodal micrometastasis. J Thorac Cardiovasc Surg 1996; 112:623-30.
3. Ku NN. Pathologic examination of sentinel lymph nodes in breast cancer. Surg Oncol Clin N Am. 1999; 8:469-79.
4. Chong CF, Leong KL, Lim TK, et al. Comparison of clinical with pathological nodal staging from systematic mediastinal lymph node dissection in early stage non-small cell lung cancer. Singapore Med J (In Press).
5. Winton T, Livingston R, Johnson D, et al; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus Cisplatin
vs. Observation in Resected Non¨CSmall-Cell Lung Cancer. N Engl J Med. 2005;352:258.
I read with interest the recent report of two cases of ‘Russell body gastritis’ by Paik and colleagues.[1] The authors described the association of their cases with Helicobacter pylori infection, and proposed that chronic infection by this organism may have caused the overproduction of immunoglobulins by the plasma cells leading to the conspicuous Russell body formation. The original report of Russell body g...
I read with interest the recent report of two cases of ‘Russell body gastritis’ by Paik and colleagues.[1] The authors described the association of their cases with Helicobacter pylori infection, and proposed that chronic infection by this organism may have caused the overproduction of immunoglobulins by the plasma cells leading to the conspicuous Russell body formation. The original report of Russell body gastritis was also associated with Helicobacter infection,[2] as was a
more recent additional case documented by Ensari and colleagues.[3] In contrast, the cases reported by Erbersdobler et al, and by Drut and Olenchuk, were negative for Helicobacter pylori.[4,5]
We recently documented a similar inflammatory process involving the uterine cervix in a 46-year female presenting with an abnormal screening Pap smear.[6] No specific infective organism was identified and the lesion appeared to resolve spontaneously in that follow up Pap smear and
colposcopy were negative. A further example of non-gastric Russell body rich inflammation was described in a patient with Barrett’s oesophagus.[7] No organisms were documented in this patient. Therefore it would appear that not all cases of Russell body gastritis are associated with
Helicobacter infection, and that Russell body-rich inflammatory infiltrates may involve mucosal sites other than the stomach. The significance of this unusual reactive process remains uncertain. Interestingly, one of the patients with Russell body gastritis was also HIV-positive,[5] but none of the other cases appears to have been associated with immunosuppression.
References
1. Paik S, Kim S-H, Kim J-H, Yang WI, Lee YC. Russell body gastritis associated with Helicobacter pylori infection: a case report. J Clin Pathol 2006; 59: 1316-9.
2. Tazawa K, Tsutsumi Y. Localised accumulation of Russell body-containing plasma cells in gastric mucosa with Helicobacter pylori infection: ‘Russell body gastritis’. Pathol Int 1998; 48: 242-4.
3. Ensari A, Savas B, Okcu Heper A, Kuzu I, Idilman R. An unusual presentation of Helicobacter pylori infection: so-called “Russell body gastritis’. Virchows Arch 2005; 446: 463-6.
4. Erbersdobler A, Petri S, Lock G. Russell body gastritis: an unusual, tumor-like lesion of the gastric mucosa. Arch Pathol Lab Med 2004; 128: 915-7.
5. Drut R, Olenchuk AB. Images in pathology. Russell body gastritis in an HIV-positive patient. Int J Surg Pathol 2006; 14: 141-2.
6. Stewart CJR, Leake R. Reactive plasmacytic infiltration with numerous Russell bodies involving the uterine cervix: ‘Russell body cervicitis’. Pathology 2006; 38: 177-9.
7. Rubio CA. Mott cell (Russell bodies) Barrett’s oesophagitis. In Vivo 2005; 19: 1097-1100.
M. Stanley has summarized and reviewed the importance of the recently available human papillomavirus (HPV) vaccine 1. In addition to this summary, I would like to stress the importance of the significant education initiatives that will be necessary to implement the success of the HPV vaccination. Yes, the vaccination may have the ability to reduce up to 70% of the HPV-associated cervical cancers...
M. Stanley has summarized and reviewed the importance of the recently available human papillomavirus (HPV) vaccine 1. In addition to this summary, I would like to stress the importance of the significant education initiatives that will be necessary to implement the success of the HPV vaccination. Yes, the vaccination may have the ability to reduce up to 70% of the HPV-associated cervical cancers we know today, however variability in socidemographic characteristics, confusion over the sexually transmissible nature of the disease and the education of health-
care workers and the media are crucial factors in making the genesis of this vaccination program successful. Along with the continuation of the gold standard PAP smear/test the new HPV vaccine shows considerable promise to help reduce and/or eradicate many cervical cancers 2. That said, HPV vaccination is also a double edged sword. The more complicated ethical reality of health care disparities and parental consent for childhood vaccination may detract from an effective vaccination program. Time will tell.
References: 1 Stanley M. Prophylactic HPV Vaccines. Published online 26 Jan 2007; J. Clin. Pathol. doi:10.1136/jcp.2006.040568
2 Dekker AH. Fostering acceptance of human papillomavirus vaccines. J Am Osteopath Assoc. 2006 ;106(3 Suppl 1):S14-8.
We are writing with respect to the following article: S Badvie, A Hanna-Morris, HJN Andreyev, P Cohen, S Saini, and TG Allen-Mersh A “field change” of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma. J Clin Pathol 2006:59: 942-946. We agree with the authors’ main conclusion that their findings are consistent with a field change of inhibited apoptosis in mucosa adjacent...
We are writing with respect to the following article: S Badvie, A Hanna-Morris, HJN Andreyev, P Cohen, S Saini, and TG Allen-Mersh A “field change” of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma. J Clin Pathol 2006:59: 942-946. We agree with the authors’ main conclusion that their findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma. However, we do take issue with their statements in the Introduction and Discussion that “...during colorectal carcinogenesis, a field change in apoptosis has not been reported.” Previous publications 1-5 also have reported field changes of increased apoptosis resistance in the non-neoplastic colonic mucosa in colon carcinogenesis. Nevertheless, the report by Badvie et al. complements these earlier reports by showing increased expression of the anti-apoptotic protein Bcl-xL, a result not previously reported, and is thus a worthwhile addition to our understanding of field defects in colorectal cancer.
References:
1 Payne CM, Bernstein H, Bernstein C, et al. The role of apoptosis in biology and pathology. J Ultrastruct Path 1995;19:221-48.
2 Garewal H, Bernstein H, Bernstein C, et al. Reduced bile-acid induced apoptosis in “normal” colorectal mucosa: a biomarker for cancer risk. Cancer Res 1996;56:1480-3.
3 Bernstein C, Bernstein H, Garewal H, et al. Resistance to bile acid-induced apoptosis in "normal" colorectal mucosa and its association with cancer risk. Cancer Res 1999;59:2353-7.
4 Bernstein H, Holubec H, Payne CM, et al. Patchy field defects of apoptosis resistance and dedifferentiation characterize flat mucosa of colon cancer patients. Annals of Surg Oncol 2002;9:505-17.
5 Bernstein H, Holubec H, Bernstein C, et al. Reduced Pms2 in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence. Appl Immunohistochem Mol Morphol 2006;14:166-72.
The world literature clearly recognises the role of the
bone marrow trephine (BMT) biopsy in the investigation of haematological disorders and its flexibility in providing both diagnostic and prognostic information, an example of which appeared in the August edition of this journal This
article gives an excellent account of the methodology employed and the accompanying illustrations clearly demonstrate th...
The world literature clearly recognises the role of the
bone marrow trephine (BMT) biopsy in the investigation of haematological disorders and its flexibility in providing both diagnostic and prognostic information, an example of which appeared in the August edition of this journal This
article gives an excellent account of the methodology employed and the accompanying illustrations clearly demonstrate the results of the wide array of investigations undertaken.
The authors talk about the use of resin embedding media
noting that ‘resin embedding and semi-thin sections provide the best morphology; there have been questions on preservation of antigens and nucleic acids. However, RNA preservation and suitability for ISH analyses of mRNA is not
clear’. They also discuss the need for specialised technology and skill and the additional associated costs. For these reasons the authors felt that the wax embedding would be their method of choice, the principles of
their approach being that the results gave excellent morphology without compromising preservation of antigens and nucleic acids. They also required the method to be simple and integrated with standard processing schedules and for it to be inexpensive and non-toxic.
We have been able to meet all of these criteria with the
added benefit of superior morphology by using Methyl Methacrylate (MMA) as the embedding medium. The reagent is cheap (<£8.00 for 500ml), easy to dispose of safely as an inert solid, and easily sectioned using disposable glass knives. There are several advantages to this practice in that the need for decalcification is greatly reduced and greater support of the tissue facilitates the routine production of 1-2ìm sections, thereby improving the quality of cell morphology on histological sections, within 24 hours of receipt.
The choice of resin is critical. Methyl methacrylate
provides a stable and reliable embedding medium which has the added benefit of being readily removed from sections and thus does not inhibit the use of either conventional or immunohistochemical staining methods. We reciprocate in
regular use, the range of antibodies demonstrated by Naresh et al. We also can demonstrate kappa and lambda light chains using ISH in trephines embedded in MMA.
As they authors rightly conclude, the ideal method for
handling BMT specimens should be worked out at each institution. In Aberdeen we have found that initial fixation in 10% NBF followed by six hours in EDTA-NBF provides excellent morphology. Specimens are dehydrated overnight on an automated tissue processor, which is also has the facility to process specimens for EM, and embedded the following morning in fresh MMA. Polymerisation takes three hours thus specimens received late afternoon are embedded, cut and sectioned by the following lunch time. Urgent
requests for ICC can be dealt with the same day and the results available within forty eight hours.
We also find that technical staff easily adapt to
sectioning resin embedded material and the staining methods, dye based and immunohistological, are identical to those employed for wax embedded tissue. Antigen retrieval methods do not need to be changed and the ISH techniques required only minimal adaptation to the manufacturer’s instructions.
The results of both the Hammersmith protocol and that used in Aberdeen are comparable; the biggest advantage of our method must be the reduction in turnaround time of BMT specimens.
We read with interest the study reported by Palmieri et al in the January 10th issue of this journal.1 In their study, serum calcium, PTH and 25(OH)D levels were measured prospectively in 279 Caucasian women with breast cancer, 75 of whom had locally advanced or metastatic disease, but patients receiving bisphosphonates were excluded. Overall, the authors found that women with early-stage breast c...
We read with interest the study reported by Palmieri et al in the January 10th issue of this journal.1 In their study, serum calcium, PTH and 25(OH)D levels were measured prospectively in 279 Caucasian women with breast cancer, 75 of whom had locally advanced or metastatic disease, but patients receiving bisphosphonates were excluded. Overall, the authors found that women with early-stage breast cancer had significantly higher 25(OH)D and lower PTH than those with advanced disease, in keeping with experimental data indicating direct inhibition of parathyroid function by 25(OH)D itself.2 That the authors found no difference in serum calcium levels between the two groups is consistent with unaltered coupling of extracellular calcium concentrations to PTH secretion by the calcium-sensing receptor.3
We have prospectively assessed the same parameters in 45 patients with progressive bone metastases while on bisphosphonate therapy (pamidronate or clodronate) for a median interval of 20 months. We also found that 25(OH)D levels were low in many patients. However, we found that serum calcium levels were elevated compared to age-matched controls. Moreover, PTH levels did not show the same coupling to 25-hydroxyvitamin D, but were elevated among those with low normal calcium, irrespective of vitamin D status. When given to normocalcemic individuals, bisphosphonates are known to provoke a short-lived hyperparathyroid response to drug-induced hypocalcemia4, but the long-term effects of high-dose bisphosphonates are little studied. If there is a tendency toward chronic secondary hyperparathyroidism amongst metastatic breast cancer survivors on long-term bisphosphonates, even when serum calcium is within the normal range, then maintenance of a ‘normal’ 25OHD level is important. At first glance, this would appear to be a simple matter of recommending a daily supplement, but considerable controversy now surrounds the adequacy of current recommendations. Some authorities are now suggesting that 25OHD levels of 75 nmol/L be considered the minimum for optimal health outcomes, a value that may require more than 2000 IU/day to achieve.5
We are currently investigating further the role of Vitamin D in metastatic breast cancer patients with bone involvement to determine if it can act as an adjunct to bisphosphonate therapy in these patients and enhance the benefits of bisphosphonates as well as investigating its
potential cytostatic role in metastatic bone disease.6 This remains an interesting and challenging area of research in breast cancer patients with advanced metastatic bone disease.
References:
1 Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Path.2006;59;1334-1336.
2 Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int. 2006 Aug;70(4):654-9.
3 Chattopadhyay N, Brown EM. Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing. Mol Genet Metab. 2006 Nov;89(3):189-202.
4 Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol. 2006 Jun;17(6):897-907.
5 Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. Review
6 Wigington DP, Strugnell SA, Knutson JC. Pamidronate and 1,24(S)-dihydroxyvitamin D2 synergistically inhibit the growth of myeloma, breast and prostate cancer cells. Anticancer Res. 2005;25:1909-17.
We read with interest the case report of an adenocarcinoma arising in a gastrocystoplasty [1]. The authors also mention another report of a transitional cell carcinoma developing within a gastrocystoplasty [2] . We would like to point out however that a signet ring cell variant of adenocarcinoma within a gastrocystoplasty has also been described [3]. Briefly a 36-year-old man presented with renal failure...
We read with interest the case report of an adenocarcinoma arising in a gastrocystoplasty [1]. The authors also mention another report of a transitional cell carcinoma developing within a gastrocystoplasty [2] . We would like to point out however that a signet ring cell variant of adenocarcinoma within a gastrocystoplasty has also been described [3]. Briefly a 36-year-old man presented with renal failure having undergone a gastrocystoplasty for the treatment of a neuropathic bladder fourteen years earlier. He was subsequently found to have an anaplastic signet ring cell carcinoma which was invading the muscularis propria of both the gastric and vesical segments at the anastomosis and extended into the intramural segment of the wall of the left ureter. These observations would suggest that tumour formation is a late, but significant complication of gastrocystoplasty. Sixty cases of carcinoma formation within augmentation cystoplasties have now been described and there is evidence to suggest that the enterocystoplasties are genetically unstable and have an inherent potential for tumour formation [4-6]. Furthermore,
tumours arising within enterocystoplasties are often aggressive, have a high mortality and are not usually detected by routine follow up cystoscopy [7].
There is some evidence to indicate that histological changes characteristic of chronic inflammation, metaplasia, and dysplasia as well as benign and malignant neoplasms may be more common in gastrocystoplasties than in either colocystoplasties or ileocystoplasties [8,9]. We agree with the authors that patients with a gastrocystoplasty should be followed up long term but would suggest that such patients
should be informed of the potential risks of long term malignant transformation before undergoing the procedure. We would also suggest that it may be worthwhile to determine whether chromosomal abnormalities at the gastrovesical anastomosis may be useful in identifying those patients most at risk from malignant transformation.
References:
1. Balachandra B, Swanson PE, Upton MP, Yeh MM. Adenocarcinoma arising in a gastrocystoplasty. J Clin Pathol 2007; 60: 85-7.
2. Qiu H, Kordunskaya S, Yantiss RK. Transitional cell carcinoma arising in the gastric remnant following gastrocystoplasty: a case report and review of the literature. Intl J Surg Pathol 2003; 11: 143-7
3. Baydar DE, Allan RW, Castellan M, Labbie A, Epstein JI. Anaplastic signet ring cell carcinoma arising in gastrocystoplasty. Urology 2005; 65: 1226
4. Ivil KD, Jenkins GJ, Parry EM, Parry JM, Stephenson TP. Identification of early p53 mutations in clam ileocystoplasties using the restriction site mutation assay. J Urol 2003; 169 (Suppl 4): 139.
5. Ivil KD, Doak SH, Jenkins SA, Parry EM, Kynaston HG, Parry JM, Stephenson TP. Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer. Br J Cancer 2006; 94: 891-89.
6. Appanna TC, Doak SH, Jenkins SA, Kynaston HG, Stephenson TP, Parry JM. Comparative genomic hybridization (CGH) of augmentation cystoplasties. Int J Urol 2007. In Press.
7. Filmer RB, Spencer JR. Malignancies in bladder augmentations and intestinal conduits. J Urol 1990; 143: 671-8.
8. Buson H, Diaz DC, Manivel JC, Jessurun J, Dayanc M, Gonzalez R. The development of tumors in experimental gastroenterocystoplasty. J Urol 1993; 150: 730-3.
9. Little JS, Klee LW, Hoover DM, Rink RC. Long-term
histopathological changes observed in rats subjected to augmentation cystoplasty. J Urol 1994; 152: 720-4.
In the article by Wareham et al. (1) the authors discuss a case report of atypical endocarditis following innoculation of Capnocytophaga canimorsus from a dog bite, and briefly review the history and management of C. canimorsus infections. There are numerous reports describing the association between the normal flora, gram-negative rod, C. canimorsus and human cardiovascular pathology (2-6). A recent report...
In the article by Wareham et al. (1) the authors discuss a case report of atypical endocarditis following innoculation of Capnocytophaga canimorsus from a dog bite, and briefly review the history and management of C. canimorsus infections. There are numerous reports describing the association between the normal flora, gram-negative rod, C. canimorsus and human cardiovascular pathology (2-6). A recent report suggests that C. canimorsus may escape the immune system by interfering with TNF-alpha expression and NO induction resulting in an insufficent proinflammatory
response (7).
Yet infections aside, dog bites account for 12th leading cause of non -fatal injuries (all ages) in the United States (8). Thus, the human suffering alone (17 deaths, 6000 hospitalizations, > 330,000 emergency
department visits a year) and the associated economic impacts justify further efforts to prevent dog bites (9).
In conclusion, the first documented report of a C. canimorsus infection in a rabbit inflicted with a dog bite (10) further highlights the need for developing a comprehensive bite prevention program (11), and
better laboratory methods for accurate diagnosis (12).
References:
1. Wareham DW, Michael JS, Warwick S, Whitlock P, Wood A, Das SS. The
dangers of dog bites. J Clin Pathol. 2007 Mar;60(3):328-329.
3. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, Kohler
RB. Unidentified gram-negative rod infection. A new disease of man. Ann
Intern Med. 1977 Jan;86(1):1-5.
4. Frigiola A, Badia T, Lovato R, Cogo A, Fugazzaro MP, Lovisetto R,
Di Donato M. Infective endocarditis due to Capnocytophaga canimorsus. Ital
Heart J. 2003 Oct;4(10):725-7.
5. Shankar PS, Scott JH, Anderson CL. Atypical endocarditis due to
gram-negative bacillus transmitted by dog bite. South Med J. 1980
Dec;73(12):1640-1.
6. Lion C, Escande F, Burdin JC. Capnocytophaga canimorsus infections
in human: review of the literature and cases report. Eur J Epidemiol. 1996
Oct;12(5):521-33. Review.
7. Shin H, Mally M, Kuhn M, Paroz C, Cornelis GR. Escape from immune
surveillance by Capnocytophaga canimorsus. J Infect Dis. 2007 Feb
1;195(3):375-86.
8. Sosin DM, Sacks JJ, Sattin RW. Causes of non-fatal injuries in the
United States, 1986. Accid. Anal. Prev. 1992; 24:685-687.
9. Quinlan KP, Sacks JJ. Hospitalizations for Dog Bite Injuries
[letter] JAMA 1999; 281:232-233.
10. van Duijkeren E, van Mourik C, Broekhuizen M, Leuven M, Gaastra W,
Houwers D. First documented Capnocytophaga canimorsus infection in a
species other than humans.
Vet Microbiol. 2006 Nov 26;118(1-2):148-50.
11. AVMA Task Force on Canine Aggression and Human-Canine
Interactions. A community approach to dog bite prevention. JAVMA 2001;
218: 1732-1749.
The histopathological assessment of prognostic factors in rectal cancer is important in guiding management. One of these factors is the circumferential resection margin (CRM). The involvement of CRM by tumour indicates a high risk of local recurrence, and is also an indicator of the quality of surgery performed1. Eid et al2 attempted to investigate the
effects of processing variability on the assessment of...
The histopathological assessment of prognostic factors in rectal cancer is important in guiding management. One of these factors is the circumferential resection margin (CRM). The involvement of CRM by tumour indicates a high risk of local recurrence, and is also an indicator of the quality of surgery performed1. Eid et al2 attempted to investigate the
effects of processing variability on the assessment of lateral (circumferential) resection margins in rectal cancer, however, there are several issues which raise concern.
The usefulness in measuring the longest perpendicular resection margin is dubious. Surely it is the nearest distance of tumour to the CRM, which holds the relevant prognostic information. It would have been more useful had the authors detailed whether the changes in the distance of the tumour to the CRM had made any difference to the pathological staging, and thus, were of clinical significance.
The selection of the duration of formalin fixation, in particular the longer period of 7 days, used to compare artefactual changes is a curiosity. Although there are no guidelines to indicate the optimum duration colorectal cancer specimens have to be immersed in formalin prior
to dissection, with increasing pressure to improve turnaround times and meet deadlines, it would be a surprise that they languish in formalin for up to 7 days before examination by a histopathologist. It is also best to
avoid over-fixation in formalin as this may cause irreversible alteration in protein structures, which may be resistant to antigen unmasking techniques, thus compromising immunohistochemical studies, when required.
It was not made clear why the authors chose to use fresh control specimens when their study specimens had at least 4 days of formalin fixation prior to dissection. Moreover, the authors failed to explain the rationale of sectioning the fresh control specimens into smaller pieces of 10mm lengths and why the duration of formalin fixation of these pieces was different to the study specimens. The authors also appear to investigate a different variable in their control and study specimens, longitudinal and transverse measurements, respectively. Thus, the comparison of control and study specimens is tenuous.
The paper’s title was misleading and alluded to processing variability, however, the only variable studied is the duration of formalin fixation. There are several steps involved in the preparation of a tissue sample for histological examination. Generally, it encompasses
fixation (usually by formalin), processing and embedding (the paraffin wax technique is the commonest) and sectioning. Contrary to the facts presented by the authors, formalin does not cause tissue shrinkage as a result of dehydration; it works by cross-linking proteins which results in firmness of the tissue. Tissue dehydration occurs during the processing stage whereby the tissue is subjected to progressive increased concentrations of ethanol. Furthermore, the authors gave no description of the processing technique used in their study and it is unclear where the rehydration stage, as described, takes place. It is therefore impossible to critically analyse their technique and accept their unexpected finding of tissue expansion.
Last but not least, it is a concern that the assessment of CRM may be suboptimal by the very economical application of yellow ink to the specimen illustrated in Figure 1. This appears to imply that tumour growth is restricted to a particular wall, when in actuality, many rectal cancers
are circumferential. It is certainly not possible to predict the location and depth of tumour invasion prior to sectioning. The practice illustrated by the authors is not in accordance with the Royal College of Pathologists minimum dataset for colorectal cancer, which recommends painting the
entire CRM with silver nitrate or India ink prior to dissection.
As there is a paucity of literature that examines the effects of formalin fixation on the histopathological assessment of CRM, the authors’ effort in attempting to address this is commendable, however, the study methodology and finding do not stand up to scrutiny.
References
1. National Minimum Dataset for Colorectal Cancer. The Royal College of Pathologists 1998.
2. Eid I, El-Muhtaseb MS, Mukherjee R, et al. Histological processing variability in the determination of lateral resection margins in rectal cancer. J Clin Pathol 2007; 60:593-595.
Dear Editor,
In the current report by Nowicki et al. the authors review and discuss the probable role of substance P in childhood leukemias and solid bone cancers, and the use of substance P antagonists for treatment (1). As reviewed by the authors, there is much evidence to support a role for substance P in carcinogenesis. Others have suggested substance P may induce mitogenesis through activation of neurokinin-1 recep...
Dear Editor
We read with interest the article by Mescoli et al. on the high prevalence of isolated tumours cells in regional lymph nodes from pN0 colorectal cancer (CRC). [1] Based on a detailed study of resected lymph nodes, Mescoli et al reported that more than 50% of pN0-CRC patients have isolated tumour cells (ITC) in the mesenteric lymph nodes and ITC status significantly correlated with cancer stage and vascular c...
Dear Editor
I read with interest the recent report of two cases of ‘Russell body gastritis’ by Paik and colleagues.[1] The authors described the association of their cases with Helicobacter pylori infection, and proposed that chronic infection by this organism may have caused the overproduction of immunoglobulins by the plasma cells leading to the conspicuous Russell body formation. The original report of Russell body g...
Dear Editor,
M. Stanley has summarized and reviewed the importance of the recently available human papillomavirus (HPV) vaccine 1. In addition to this summary, I would like to stress the importance of the significant education initiatives that will be necessary to implement the success of the HPV vaccination. Yes, the vaccination may have the ability to reduce up to 70% of the HPV-associated cervical cancers...
Dear Editor
We are writing with respect to the following article: S Badvie, A Hanna-Morris, HJN Andreyev, P Cohen, S Saini, and TG Allen-Mersh A “field change” of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma. J Clin Pathol 2006:59: 942-946. We agree with the authors’ main conclusion that their findings are consistent with a field change of inhibited apoptosis in mucosa adjacent...
Dear Editor
The world literature clearly recognises the role of the bone marrow trephine (BMT) biopsy in the investigation of haematological disorders and its flexibility in providing both diagnostic and prognostic information, an example of which appeared in the August edition of this journal This article gives an excellent account of the methodology employed and the accompanying illustrations clearly demonstrate th...
Dear Editor
We read with interest the study reported by Palmieri et al in the January 10th issue of this journal.1 In their study, serum calcium, PTH and 25(OH)D levels were measured prospectively in 279 Caucasian women with breast cancer, 75 of whom had locally advanced or metastatic disease, but patients receiving bisphosphonates were excluded. Overall, the authors found that women with early-stage breast c...
Dear Editor
We read with interest the case report of an adenocarcinoma arising in a gastrocystoplasty [1]. The authors also mention another report of a transitional cell carcinoma developing within a gastrocystoplasty [2] . We would like to point out however that a signet ring cell variant of adenocarcinoma within a gastrocystoplasty has also been described [3]. Briefly a 36-year-old man presented with renal failure...
Dear Editor
In the article by Wareham et al. (1) the authors discuss a case report of atypical endocarditis following innoculation of Capnocytophaga canimorsus from a dog bite, and briefly review the history and management of C. canimorsus infections. There are numerous reports describing the association between the normal flora, gram-negative rod, C. canimorsus and human cardiovascular pathology (2-6). A recent report...
Dear Editor
The histopathological assessment of prognostic factors in rectal cancer is important in guiding management. One of these factors is the circumferential resection margin (CRM). The involvement of CRM by tumour indicates a high risk of local recurrence, and is also an indicator of the quality of surgery performed1. Eid et al2 attempted to investigate the effects of processing variability on the assessment of...
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